Amyloid-beta precursor protein (APP) is a type I transmembrane glycoprotein that undergoes regulated proteolytic processing to generate soluble ectodomains, membrane-tethered C-terminal fragments, amyloid-beta peptides, and the APP intracellular domain. Full-length APP acts at the neuronal cell surface and in secretory/endocytic compartments, where it contributes to cell adhesion, synaptogenesis, neurite outgrowth, axonogenesis, and interactions with extracellular matrix ligands. Alternative splice isoforms differ in inclusion of the Kunitz protease inhibitor domain, giving APP751/770 protease-inhibitor activity that is absent from neuronal APP695. APP and amyloid-beta fragments bind transition metals, especially copper and zinc, linking the ectodomain and cleavage products to metal homeostasis and redox biology. In Alzheimer disease, familial APP variants and APP dosage alter amyloidogenic processing and the production or aggregation of amyloid-beta species.
Curated functional classes representing distinct biological activities. These may be splice variants, cleavage products, or other forms with different functions.
APP_695_NEURONALAPP_KPI_CONTAININGAPP_SAPP_ALPHAPRO_0000000088 (residues 18-687) APP_SAPP_BETAPRO_0000000089 (residues 18-671) APP_ABETA42PRO_0000000092 (residues 672-713) APP_ABETA40PRO_0000000091 (residues 672-711) APP_AICDPRO_0000000093, PRO_0000000094, PRO_0000000095 (residues 712-770 / 714-770 / 721-770) APP_N_APPPRO_0000381966 (residues 18-286) | GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0007409 axonogenesis | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation. Full-length APP regulates axon development. APP knockout mice show defects in axonogenesis. sAPPalpha promotes neurite outgrowth while full-length APP with Fe65/Mena inhibits branching to ensure directional growth. Reason: Core biological process. Well-supported by knockout studies and mechanistic understanding. |
| GO:0007417 central nervous system development | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference (IBA) from GO_REF:0000033. IBA annotations undergo extensive phylogenetic review and are generally reliable. Reason: IBA annotation supported by phylogenetic analysis. |
| GO:0005769 early endosome | IBA GO_REF:0000033 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P05067). Reason: Well-documented localization consistent with APP biology. |
| GO:0005102 signaling receptor binding | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference (IBA) from GO_REF:0000033. IBA annotations undergo extensive phylogenetic review and are generally reliable. Reason: IBA annotation supported by phylogenetic analysis. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P05067). Reason: Well-documented localization consistent with APP biology. |
| GO:0030546 signaling receptor activator activity | IBA GO_REF:0000033 | ACCEPT | Summary: Abeta42 activates FPR2 (formyl peptide receptor 2), inducing chemotaxis and oxidant stress in phagocytes (PMID:11316806). Note: this is primarily an Abeta cleavage product function. Reason: Supported by literature, though applies to Abeta rather than full-length APP. |
| GO:0005794 Golgi apparatus | IBA GO_REF:0000033 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P05067). Reason: Well-documented localization consistent with APP biology. |
| GO:0045121 membrane raft | IBA GO_REF:0000033 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P05067). Reason: Well-documented localization consistent with APP biology. |
| GO:0009986 cell surface | IBA GO_REF:0000033 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P05067). Reason: Well-documented localization consistent with APP biology. |
| GO:0004867 serine-type endopeptidase inhibitor activity | IEA GO_REF:0000120 | ACCEPT | Summary: ISOFORM-SPECIFIC: KPI-containing isoforms (APP751/770) only. The Kunitz protease inhibitor domain is absent from the neuronal APP695 isoform. Reason: IEA annotation consistent with known APP biology. Note isoform specificity. |
| GO:0005576 extracellular region | IEA GO_REF:0000044 | ACCEPT | Summary: IEA annotation. Secreted sAPPalpha/beta and Abeta are found in extracellular region. Reason: IEA annotation consistent with known APP functions. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: AICD translocates to nucleus with Fe65 and Tip60 for transcriptional regulation. However, this remains controversial. Reason: IEA annotation consistent with known APP functions. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation. APP cytoplasmic domain interacts with multiple adaptor proteins. Reason: IEA annotation consistent with known APP functions. |
| GO:0005769 early endosome | IEA GO_REF:0000044 | ACCEPT | Summary: IEA annotation. APP is processed in endosomes where BACE1 cleavage occurs. Reason: IEA annotation consistent with known APP trafficking. |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000044 | ACCEPT | Summary: IEA annotation. APP is synthesized and processed through ER. Reason: IEA annotation consistent with known APP trafficking. |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000044 | ACCEPT | Summary: IEA annotation. APP transits through Golgi during maturation. Reason: IEA annotation consistent with known APP trafficking. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: IEA annotation. Full-length APP is a type I transmembrane protein at plasma membrane. Reason: IEA annotation consistent with known APP functions. |
| GO:0005905 clathrin-coated pit | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation. APP is internalized via clathrin-mediated endocytosis. Reason: IEA annotation consistent with known APP trafficking. |
| GO:0006897 endocytosis | IEA GO_REF:0000043 | ACCEPT | Summary: IEA annotation. APP undergoes internalization via endocytosis. Reason: IEA annotation consistent with known APP functions. |
| GO:0006915 apoptotic process | IEA GO_REF:0000043 | ACCEPT | Summary: CLEAVAGE PRODUCT DEPENDENT: Abeta induces apoptosis (neurotoxic), while sAPPalpha is neuroprotective. Full-length APP itself has dual roles depending on processing pathway. Reason: IEA annotation consistent with APP biology but note cleavage product specificity. |
| GO:0007155 cell adhesion | IEA GO_REF:0000043 | ACCEPT | Summary: IEA annotation. Full-length APP functions as a cell adhesion molecule via trans-dimerization. Reason: Core function of full-length APP. |
| GO:0007219 Notch signaling pathway | IEA GO_REF:0000043 | REMOVE | Summary: APP is not a component of the Notch signaling pathway. This IEA annotation likely arises because APP and Notch are both substrates of gamma-secretase (presenilin), but sharing an enzyme does not make APP part of the Notch pathway. APP has its own distinct signaling pathway via AICD. Reason: APP is a substrate of gamma-secretase but is NOT a participant in Notch signaling. The connection is only that they share the same protease. This is an incorrect annotation that should be removed. |
| GO:0008201 heparin binding | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation. APP ectodomain binds heparin and heparan sulfate proteoglycans. Reason: IEA annotation consistent with known APP functions. |
| GO:0009986 cell surface | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation. Full-length APP is a type I transmembrane protein at cell surface. Reason: IEA annotation consistent with known APP localization. |
| GO:0010604 positive regulation of macromolecule metabolic process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: IEA annotation for positive regulation of macromolecule metabolic process. This is extremely broad and does not provide useful functional information about APP. Reason: Too broad to be informative. Over-annotation. |
| GO:0016020 membrane | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation. Full-length APP is a type I transmembrane protein. Reason: IEA annotation consistent with known APP localization. |
| GO:0030414 peptidase inhibitor activity | IEA GO_REF:0000043 | ACCEPT | Summary: ISOFORM-SPECIFIC: KPI-containing isoforms (APP751/770) only. The Kunitz protease inhibitor domain is absent from neuronal APP695. Reason: IEA annotation consistent with known APP biology. Note isoform specificity. |
| GO:0030426 growth cone | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation. APP is localized to growth cones and regulates axon guidance. Reason: IEA annotation consistent with known APP localization and function. |
| GO:0031091 platelet alpha granule | IEA GO_REF:0000117 | ACCEPT | Summary: IEA annotation. APP is expressed in platelets and stored in alpha granules. Reason: IEA annotation consistent with known APP expression. |
| GO:0031410 cytoplasmic vesicle | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation. APP is transported in vesicles along axons. Reason: IEA annotation consistent with known APP trafficking. |
| GO:0043005 neuron projection | IEA GO_REF:0000117 | ACCEPT | Summary: IEA annotation. APP is transported to and localized in neuron projections. Reason: IEA annotation consistent with known APP localization. |
| GO:0043204 perikaryon | IEA GO_REF:0000044 | ACCEPT | Summary: IEA annotation. APP is found in neuronal cell bodies. Reason: IEA annotation consistent with known APP localization. |
| GO:0046872 metal ion binding | IEA GO_REF:0000043 | ACCEPT | Summary: IEA annotation. APP binds copper and zinc via its ectodomain and regulates metal homeostasis. Reason: Core function of APP. Well documented. |
| GO:0046914 transition metal ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: IEA annotation. APP binds copper and zinc (transition metals) via its ectodomain. Reason: Core function of APP. Well documented. |
| GO:0051246 regulation of protein metabolic process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: IEA annotation for regulation of protein metabolic process. This is very broad and does not provide useful functional information about APP. Reason: Too broad to be informative. Over-annotation. |
| GO:0140677 molecular function activator activity | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: IEA annotation for molecular function activator activity. This is extremely broad and does not specify what molecular function APP activates. Not informative. Reason: Too broad to be informative. Over-annotation. |
| GO:0005515 protein binding | IPI PMID:10677483 Human aspartic protease memapsin 2 cleaves the beta-secretas... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. BACE1 (memapsin 2) cleaves APP at the beta-secretase site. Functional interaction for APP processing. Reason: Generic protein binding uninformative - the specific interaction is with BACE1. Supporting Evidence: PMID:10677483 Human aspartic protease memapsin 2 cleaves the beta-secretase site of beta-amyloid precursor protein. |
| GO:0005515 protein binding | IPI PMID:10681545 beta-Amyloid(1-42) binds to alpha7 nicotinic acetylcholine r... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:10681545 beta-Amyloid(1-42) binds to alpha7 nicotinic acetylcholine receptor with high affinity. |
| GO:0005515 protein binding | IPI PMID:11278849 beta -Amyloid peptide-induced apoptosis regulated by a novel... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:11278849 2001 Feb 20. beta -Amyloid peptide-induced apoptosis regulated by a novel protein containing a g protein activation module. |
| GO:0005515 protein binding | IPI PMID:11297421 Apolipoprotein A-I directly interacts with amyloid precursor... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:11297421 Apolipoprotein A-I directly interacts with amyloid precursor protein and inhibits A beta aggregation and toxicity. |
| GO:0005515 protein binding | IPI PMID:11724784 Jun NH2-terminal kinase (JNK) interacting protein 1 (JIP1) b... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:11724784 Nov 27. Jun NH2-terminal kinase (JNK) interacting protein 1 (JIP1) binds the cytoplasmic domain of the Alzheimer's beta-amyloid precursor protein (APP). |
| GO:0005515 protein binding | IPI PMID:11877420 Tyrosine phosphorylation of the beta-amyloid precursor prote... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:11877420 2002 Mar 4. Tyrosine phosphorylation of the beta-amyloid precursor protein cytoplasmic tail promotes interaction with Shc. |
| GO:0005515 protein binding | IPI PMID:12485888 Signal transduction through tyrosine-phosphorylated carboxy-... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:12485888 Signal transduction through tyrosine-phosphorylated carboxy-terminal fragments of APP via an enhanced interaction with Shc/Grb2 adaptor proteins in reactive astrocytes of Alzheimer's disease brain. |
| GO:0005515 protein binding | IPI PMID:12901838 Presenilin-1 interacts directly with the beta-site amyloid p... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:12901838 Presenilin-1 interacts directly with the beta-site amyloid protein precursor cleaving enzyme (BACE1). |
| GO:0005515 protein binding | IPI PMID:15896298 In cerebrospinal fluid ER chaperones ERp57 and calreticulin ... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:15896298 In cerebrospinal fluid ER chaperones ERp57 and calreticulin bind beta-amyloid. |
| GO:0005515 protein binding | IPI PMID:16027166 BRI2 interacts with amyloid precursor protein (APP) and regu... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:16027166 2005 Jul 18. BRI2 interacts with amyloid precursor protein (APP) and regulates amyloid beta (Abeta) production. |
| GO:0005515 protein binding | IPI PMID:16049941 A pilot proteomic study of amyloid precursor interactors in ... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:16049941 A pilot proteomic study of amyloid precursor interactors in Alzheimer's disease. |
| GO:0005515 protein binding | IPI PMID:16174740 Neuronal sorting protein-related receptor sorLA/LR11 regulat... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:16174740 Neuronal sorting protein-related receptor sorLA/LR11 regulates processing of the amyloid precursor protein. |
| GO:0005515 protein binding | IPI PMID:16286452 Gerstmann-StrΓ€ussler-Scheinker disease amyloid protein polym... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:16286452 Nov 10. Gerstmann-StrΓ€ussler-Scheinker disease amyloid protein polymerizes according to the "dock-and-lock" model. |
| GO:0005515 protein binding | IPI PMID:16374483 Neurofibromatosis type 1 protein and amyloid precursor prote... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:16374483 Neurofibromatosis type 1 protein and amyloid precursor protein interact in normal human melanocytes and colocalize with melanosomes. |
| GO:0005515 protein binding | IPI PMID:16446437 Abeta and tau form soluble complexes that may promote self a... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:16446437 Abeta and tau form soluble complexes that may promote self aggregation of both into the insoluble forms observed in Alzheimer's disease. |
| GO:0005515 protein binding | IPI PMID:16480949 The intracellular domain of amyloid precursor protein intera... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:16480949 The intracellular domain of amyloid precursor protein interacts with flotillin-1, a lipid raft protein. |
| GO:0005515 protein binding | IPI PMID:16554819 The prolyl isomerase Pin1 regulates amyloid precursor protei... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:16554819 The prolyl isomerase Pin1 regulates amyloid precursor protein processing and amyloid-beta production. |
| GO:0005515 protein binding | IPI PMID:17112520 Aluminum inhibits proteolytic degradation of amyloid beta pe... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:17112520 Epub 2006 Nov 9. Aluminum inhibits proteolytic degradation of amyloid beta peptide by cathepsin D: a potential link between aluminum accumulation and neuritic plaque deposition. |
| GO:0005515 protein binding | IPI PMID:17709753 Amyolid precursor protein mediates presynaptic localization ... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:17709753 Amyolid precursor protein mediates presynaptic localization and activity of the high-affinity choline transporter. |
| GO:0005515 protein binding | IPI PMID:20195357 A comprehensive resource of interacting protein regions for ... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:20195357 A comprehensive resource of interacting protein regions for refining human transcription factor networks. |
| GO:0005515 protein binding | IPI PMID:20811458 Gamma-secretase activating protein is a therapeutic target f... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:20811458 Gamma-secretase activating protein is a therapeutic target for Alzheimer's disease. |
| GO:0005515 protein binding | IPI PMID:20817278 Iron-export ferroxidase activity of Ξ²-amyloid precursor prot... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:20817278 Iron-export ferroxidase activity of Ξ²-amyloid precursor protein is inhibited by zinc in Alzheimer's disease. |
| GO:0005515 protein binding | IPI PMID:20828565 An aminopeptidase from Streptomyces sp. KK565 degrades beta ... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:20828565 Epub 2010 Sep 7. An aminopeptidase from Streptomyces sp. |
| GO:0005515 protein binding | IPI PMID:21163940 Interactome mapping suggests new mechanistic details underly... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:21163940 Interactome mapping suggests new mechanistic details underlying Alzheimer's disease. |
| GO:0005515 protein binding | IPI PMID:2119582 Transforming growth factor-beta bound to soluble derivatives... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:2119582 Transforming growth factor-beta bound to soluble derivatives of the beta amyloid precursor protein of Alzheimer's disease. |
| GO:0005515 protein binding | IPI PMID:21293490 Mediator is a transducer of amyloid-precursor-protein-depend... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:21293490 Mediator is a transducer of amyloid-precursor-protein-dependent nuclear signalling. |
| GO:0005515 protein binding | IPI PMID:22730553 Open-closed motion of Mint2 regulates APP metabolism. | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:22730553 Open-closed motion of Mint2 regulates APP metabolism. |
| GO:0005515 protein binding | IPI PMID:22801501 A mutation in APP protects against Alzheimer's disease and a... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:22801501 A mutation in APP protects against Alzheimer's disease and age-related cognitive decline. |
| GO:0005515 protein binding | IPI PMID:23585889 Generation of amyloid-Ξ² is reduced by the interaction of cal... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:23585889 Generation of amyloid-Ξ² is reduced by the interaction of calreticulin with amyloid precursor protein, presenilin and nicastrin. |
| GO:0005515 protein binding | IPI PMID:24028865 Impact of the cellular prion protein on amyloid-Ξ² and 3PO-ta... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:24028865 Impact of the cellular prion protein on amyloid-Ξ² and 3PO-tau processing. |
| GO:0005515 protein binding | IPI PMID:24284412 Amyloid beta a4 precursor protein-binding family B member 1 ... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:24284412 2013 Nov 27. Amyloid beta a4 precursor protein-binding family B member 1 (FE65) interactomics revealed synaptic vesicle glycoprotein 2A (SV2A) and sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) as new binding proteins in the human brain. |
| GO:0005515 protein binding | IPI PMID:24867889 sAPP modulates iron efflux from brain microvascular endothel... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:24867889 sAPP modulates iron efflux from brain microvascular endothelial cells by stabilizing the ferrous iron exporter ferroportin. |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:25241761 Oct 9. Using an in situ proximity ligation assay to systematically profile endogenous protein-protein interactions in a pathway network. |
| GO:0005515 protein binding | IPI PMID:25959826 Quantitative interaction proteomics of neurodegenerative dis... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:25959826 2015 May 7. Quantitative interaction proteomics of neurodegenerative disease proteins. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:26496610 Oct 22. A human interactome in three quantitative dimensions organized by stoichiometries and abundances. |
| GO:0005515 protein binding | IPI PMID:29423001 Hypoxia increases amyloid-Ξ² level in exosomes by enhancing t... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:29423001 Hypoxia increases amyloid-Ξ² level in exosomes by enhancing the interaction between CD147 and Hook1. |
| GO:0005515 protein binding | IPI PMID:29578633 Probing the Mint2 Protein-Protein Interaction Network Releva... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:29578633 Probing the Mint2 Protein-Protein Interaction Network Relevant to the Pathophysiology of Alzheimer's Disease. |
| GO:0005515 protein binding | IPI PMID:30086173 TMEM30A is a candidate interacting partner for the Ξ²-carboxy... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:30086173 eCollection 2018. TMEM30A is a candidate interacting partner for the Ξ²-carboxyl-terminal fragment of amyloid-Ξ² precursor protein in endosomes. |
| GO:0005515 protein binding | IPI PMID:30538620 Visualization of Alzheimer's Disease Related Ξ±-/Ξ²-/Ξ³-Secreta... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:30538620 eCollection 2018. Visualization of Alzheimer's Disease Related Ξ±-/Ξ²-/Ξ³-Secretase Ternary Complex by Bimolecular Fluorescence Complementation Based Fluorescence Resonance Energy Transfer. |
| GO:0005515 protein binding | IPI PMID:31413325 HENA, heterogeneous network-based data set for Alzheimer's d... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:31413325 HENA, heterogeneous network-based data set for Alzheimer's disease. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:33961781 2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. |
| GO:0005515 protein binding | IPI PMID:34446781 First identification of ITM2B interactome in the human retin... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:34446781 First identification of ITM2B interactome in the human retina. |
| GO:0005515 protein binding | IPI PMID:35063084 Tau interactome maps synaptic and mitochondrial processes as... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:35063084 2022 Jan 20. Tau interactome maps synaptic and mitochondrial processes associated with neurodegeneration. |
| GO:0005515 protein binding | IPI PMID:35914814 Chr21 protein-protein interactions: enrichment in proteins i... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:35914814 Chr21 protein-protein interactions: enrichment in proteins involved in intellectual disability, autism, and late-onset Alzheimer's disease. |
| GO:0005515 protein binding | IPI PMID:35922511 A physical wiring diagram for the human immune system. | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:35922511 Aug 3. A physical wiring diagram for the human immune system. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:40205054 Apr 9. Multimodal cell maps as a foundation for structural and functional genomics. |
| GO:0005515 protein binding | IPI PMID:8855266 Association of a novel human FE65-like protein with the cyto... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:8855266 Association of a novel human FE65-like protein with the cytoplasmic domain of the beta-amyloid precursor protein. |
| GO:0005515 protein binding | IPI PMID:8887653 The phosphotyrosine interaction domains of X11 and FE65 bind... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:8887653 The phosphotyrosine interaction domains of X11 and FE65 bind to distinct sites on the YENPTY motif of amyloid precursor protein. |
| GO:0005515 protein binding | IPI PMID:9223340 Interaction between amyloid precursor protein and presenilin... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:9223340 Interaction between amyloid precursor protein and presenilins in mammalian cells: implications for the pathogenesis of Alzheimer disease. |
| GO:0005515 protein binding | IPI PMID:9338779 An intracellular protein that binds amyloid-beta peptide and... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:9338779 An intracellular protein that binds amyloid-beta peptide and mediates neurotoxicity in Alzheimer's disease. |
| GO:0005515 protein binding | IPI PMID:9461550 Fe65L2: a new member of the Fe65 protein family interacting ... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:9461550 Fe65L2: a new member of the Fe65 protein family interacting with the intracellular domain of the Alzheimer's beta-amyloid precursor protein. |
| GO:0005515 protein binding | IPI PMID:10673326 Agrin binds to beta-amyloid (Abeta), accelerates abeta fibri... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:10673326 Agrin binds to beta-amyloid (Abeta), accelerates abeta fibril formation, and is localized to Abeta deposits in Alzheimer's disease brain. |
| GO:0005515 protein binding | IPI PMID:11756426 Amyloid beta binds trimers as well as monomers of the 75-kDa... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:11756426 Dec 27. Amyloid beta binds trimers as well as monomers of the 75-kDa neurotrophin receptor and activates receptor signaling. |
| GO:0005515 protein binding | IPI PMID:15615705 CLAC binds to amyloid beta peptides through the positively c... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:15615705 2004 Dec 21. CLAC binds to amyloid beta peptides through the positively charged amino acid cluster within the collagenous domain 1 and inhibits formation of amyloid fibrils. |
| GO:0005515 protein binding | IPI PMID:17051221 Structures of human insulin-degrading enzyme reveal a new su... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:17051221 Structures of human insulin-degrading enzyme reveal a new substrate recognition mechanism. |
| GO:0005515 protein binding | IPI PMID:17116874 Blocking the apolipoprotein E/amyloid-beta interaction as a ... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:17116874 Blocking the apolipoprotein E/amyloid-beta interaction as a potential therapeutic approach for Alzheimer's disease. |
| GO:0005515 protein binding | IPI PMID:18806802 Cyclophilin D deficiency attenuates mitochondrial and neuron... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:18806802 Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease. |
| GO:0005515 protein binding | IPI PMID:22179788 The extracellular chaperone clusterin sequesters oligomeric ... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:22179788 The extracellular chaperone clusterin sequesters oligomeric forms of the amyloid-Ξ²(1-40) peptide. |
| GO:0005515 protein binding | IPI PMID:22528093 Search for amyloid-binding proteins by affinity chromatograp... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:22528093 Search for amyloid-binding proteins by affinity chromatography. |
| GO:0005515 protein binding | IPI PMID:24931469 Molecular basis of substrate recognition and degradation by ... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:24931469 2014 Jun 12. Molecular basis of substrate recognition and degradation by human presequence protease. |
| GO:0005515 protein binding | IPI PMID:25643321 Structural basis for amyloidogenic peptide recognition by so... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:25643321 Feb 2. Structural basis for amyloidogenic peptide recognition by sorLA. |
| GO:0005515 protein binding | IPI PMID:25897080 Sequential Amyloid-Ξ² Degradation by the Matrix Metalloprotea... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:25897080 2015 Apr 20. Sequential Amyloid-Ξ² Degradation by the Matrix Metalloproteases MMP-2 and MMP-9. |
| GO:0005515 protein binding | IPI PMID:26618561 Direct High Affinity Interaction between AΞ²42 and GSK3Ξ± Stim... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:26618561 Epub 2015 Dec 15. Direct High Affinity Interaction between AΞ²42 and GSK3Ξ± Stimulates Hyperphosphorylation of Tau. |
| GO:0005515 protein binding | IPI PMID:30158114 TLR5 decoy receptor as a novel anti-amyloid therapeutic for ... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:30158114 TLR5 decoy receptor as a novel anti-amyloid therapeutic for Alzheimer's disease. |
| GO:0042802 identical protein binding | IPI PMID:16286452 Gerstmann-StrΓ€ussler-Scheinker disease amyloid protein polym... | ACCEPT | Summary: IPI annotation. APP dimerization (homodimerization) is well-established and functionally relevant for cell adhesion and processing. Reason: APP homodimerization is a core function. More informative than generic protein binding. Supporting Evidence: PMID:16286452 Nov 10. Gerstmann-StrΓ€ussler-Scheinker disease amyloid protein polymerizes according to the "dock-and-lock" model. |
| GO:0042802 identical protein binding | IPI PMID:18805418 In vitro perturbation of aggregation processes in beta-amylo... | ACCEPT | Summary: IPI annotation. APP dimerization (homodimerization) is well-established and functionally relevant for cell adhesion and processing. Reason: APP homodimerization is a core function. More informative than generic protein binding. Supporting Evidence: PMID:18805418 Epub 2008 Sep 19. In vitro perturbation of aggregation processes in beta-amyloid peptides: a spectroscopic study. |
| GO:0042802 identical protein binding | IPI PMID:19549187 Quenched hydrogen/deuterium exchange NMR characterization of... | ACCEPT | Summary: IPI annotation. APP dimerization (homodimerization) is well-established and functionally relevant for cell adhesion and processing. Reason: APP homodimerization is a core function. More informative than generic protein binding. Supporting Evidence: PMID:19549187 2009 Jun 22. Quenched hydrogen/deuterium exchange NMR characterization of amyloid-beta peptide aggregates formed in the presence of Cu2+ or Zn2+. |
| GO:0042802 identical protein binding | IPI PMID:19754881 The thioflavin T fluorescence assay for amyloid fibril detec... | ACCEPT | Summary: IPI annotation. APP dimerization (homodimerization) is well-established and functionally relevant for cell adhesion and processing. Reason: APP homodimerization is a core function. More informative than generic protein binding. Supporting Evidence: PMID:19754881 2009 Sep 15. The thioflavin T fluorescence assay for amyloid fibril detection can be biased by the presence of exogenous compounds. |
| GO:0042802 identical protein binding | IPI PMID:20573181 Progressive accumulation of amyloid-beta oligomers in Alzhei... | ACCEPT | Summary: IPI annotation. APP dimerization (homodimerization) is well-established and functionally relevant for cell adhesion and processing. Reason: APP homodimerization is a core function. More informative than generic protein binding. Supporting Evidence: PMID:20573181 2010 Jun 22. Progressive accumulation of amyloid-beta oligomers in Alzheimer's disease and in amyloid precursor protein transgenic mice is accompanied by selective alterations in synaptic scaffold proteins. |
| GO:0042802 identical protein binding | IPI PMID:20818335 Neurotoxicity of Alzheimer's disease AΞ² peptides is induced ... | ACCEPT | Summary: IPI annotation. APP dimerization (homodimerization) is well-established and functionally relevant for cell adhesion and processing. Reason: APP homodimerization is a core function. More informative than generic protein binding. Supporting Evidence: PMID:20818335 Neurotoxicity of Alzheimer's disease AΞ² peptides is induced by small changes in the AΞ²42 to AΞ²40 ratio. |
| GO:0042802 identical protein binding | IPI PMID:21113149 Reversing EphB2 depletion rescues cognitive functions in Alz... | ACCEPT | Summary: IPI annotation. APP dimerization (homodimerization) is well-established and functionally relevant for cell adhesion and processing. Reason: APP homodimerization is a core function. More informative than generic protein binding. Supporting Evidence: PMID:21113149 Reversing EphB2 depletion rescues cognitive functions in Alzheimer model. |
| GO:0042802 identical protein binding | IPI PMID:21205198 Lysophosphatidylcholine modulates fibril formation of amyloi... | ACCEPT | Summary: IPI annotation. APP dimerization (homodimerization) is well-established and functionally relevant for cell adhesion and processing. Reason: APP homodimerization is a core function. More informative than generic protein binding. Supporting Evidence: PMID:21205198 2011 Jan 17. Lysophosphatidylcholine modulates fibril formation of amyloid beta peptide. |
| GO:0042802 identical protein binding | IPI PMID:21320494 Lipid matrix plays a role in Abeta fibril kinetics and morph... | ACCEPT | Summary: IPI annotation. APP dimerization (homodimerization) is well-established and functionally relevant for cell adhesion and processing. Reason: APP homodimerization is a core function. More informative than generic protein binding. Supporting Evidence: PMID:21320494 2011 Feb 12. Lipid matrix plays a role in Abeta fibril kinetics and morphology. |
| GO:0042802 identical protein binding | IPI PMID:21527912 Extracellular phosphorylation of the amyloid Ξ²-peptide promo... | ACCEPT | Summary: IPI annotation. APP dimerization (homodimerization) is well-established and functionally relevant for cell adhesion and processing. Reason: APP homodimerization is a core function. More informative than generic protein binding. Supporting Evidence: PMID:21527912 Extracellular phosphorylation of the amyloid Ξ²-peptide promotes formation of toxic aggregates during the pathogenesis of Alzheimer's disease. |
| GO:0042802 identical protein binding | IPI PMID:22200570 Effect of N-homocysteinylation on physicochemical and cytoto... | ACCEPT | Summary: IPI annotation. APP dimerization (homodimerization) is well-established and functionally relevant for cell adhesion and processing. Reason: APP homodimerization is a core function. More informative than generic protein binding. Supporting Evidence: PMID:22200570 2011 Dec 23. Effect of N-homocysteinylation on physicochemical and cytotoxic properties of amyloid Ξ²-peptide. |
| GO:0042802 identical protein binding | IPI PMID:22584060 Dimeric structure of transmembrane domain of amyloid precurs... | ACCEPT | Summary: IPI annotation. APP dimerization (homodimerization) is well-established and functionally relevant for cell adhesion and processing. Reason: APP homodimerization is a core function. More informative than generic protein binding. Supporting Evidence: PMID:22584060 Epub 2012 May 11. Dimeric structure of transmembrane domain of amyloid precursor protein in micellar environment. |
| GO:0042802 identical protein binding | IPI PMID:23103738 A comparative analysis of the aggregation behavior of amyloi... | ACCEPT | Summary: IPI annotation. APP dimerization (homodimerization) is well-established and functionally relevant for cell adhesion and processing. Reason: APP homodimerization is a core function. More informative than generic protein binding. Supporting Evidence: PMID:23103738 Epub 2012 Oct 24. A comparative analysis of the aggregation behavior of amyloid-Ξ² peptide variants. |
| GO:0042802 identical protein binding | IPI PMID:23353684 Protease-activated alpha-2-macroglobulin can inhibit amyloid... | ACCEPT | Summary: IPI annotation. APP dimerization (homodimerization) is well-established and functionally relevant for cell adhesion and processing. Reason: APP homodimerization is a core function. More informative than generic protein binding. Supporting Evidence: PMID:23353684 2013 Jan 23. Protease-activated alpha-2-macroglobulin can inhibit amyloid formation via two distinct mechanisms. |
| GO:0042802 identical protein binding | IPI PMID:23416305 Interaction between soluble AΞ²-(1-40) monomer and AΞ²-(1-42) ... | ACCEPT | Summary: IPI annotation. APP dimerization (homodimerization) is well-established and functionally relevant for cell adhesion and processing. Reason: APP homodimerization is a core function. More informative than generic protein binding. Supporting Evidence: PMID:23416305 2013 Feb 15. Interaction between soluble AΞ²-(1-40) monomer and AΞ²-(1-42) fibrils probed by paramagnetic relaxation enhancement. |
| GO:0042802 identical protein binding | IPI PMID:23551356 N-terminal domain of PyrococcusΒ furiosus l-asparaginase func... | ACCEPT | Summary: IPI annotation. APP dimerization (homodimerization) is well-established and functionally relevant for cell adhesion and processing. Reason: APP homodimerization is a core function. More informative than generic protein binding. Supporting Evidence: PMID:23551356 N-terminal domain of Pyrococcus furiosus l-asparaginase functions as a non-specific, stable, molecular chaperone. |
| GO:0042802 identical protein binding | IPI PMID:23603391 NMR characterization of the interaction of GroEL with amyloi... | ACCEPT | Summary: IPI annotation. APP dimerization (homodimerization) is well-established and functionally relevant for cell adhesion and processing. Reason: APP homodimerization is a core function. More informative than generic protein binding. Supporting Evidence: PMID:23603391 2013 Apr 18. NMR characterization of the interaction of GroEL with amyloid Ξ² as a model ligand. |
| GO:0042802 identical protein binding | IPI PMID:23907009 Isobavachalcone and bavachinin from Psoraleae Fructus modula... | ACCEPT | Summary: IPI annotation. APP dimerization (homodimerization) is well-established and functionally relevant for cell adhesion and processing. Reason: APP homodimerization is a core function. More informative than generic protein binding. Supporting Evidence: PMID:23907009 Epub 2013 Jul 29. Isobavachalcone and bavachinin from Psoraleae Fructus modulate AΞ²42 aggregation process through different mechanisms in vitro. |
| GO:0042802 identical protein binding | IPI PMID:24065130 Amyloid-Ξ² oligomers induce synaptic damage via Tau-dependent... | ACCEPT | Summary: IPI annotation. APP dimerization (homodimerization) is well-established and functionally relevant for cell adhesion and processing. Reason: APP homodimerization is a core function. More informative than generic protein binding. Supporting Evidence: PMID:24065130 Amyloid-Ξ² oligomers induce synaptic damage via Tau-dependent microtubule severing by TTLL6 and spastin. |
| GO:0042802 identical protein binding | IPI PMID:24720730 The coexistence of an equal amount of Alzheimer's amyloid-Ξ² ... | ACCEPT | Summary: IPI annotation. APP dimerization (homodimerization) is well-established and functionally relevant for cell adhesion and processing. Reason: APP homodimerization is a core function. More informative than generic protein binding. Supporting Evidence: PMID:24720730 The coexistence of an equal amount of Alzheimer's amyloid-Ξ² 40 and 42 forms structurally stable and toxic oligomers through a distinct pathway. |
| GO:0042802 identical protein binding | IPI PMID:28882996 Fibril structure of amyloid-Ξ²(1-42) by cryo-electron microsc... | ACCEPT | Summary: IPI annotation. APP dimerization (homodimerization) is well-established and functionally relevant for cell adhesion and processing. Reason: APP homodimerization is a core function. More informative than generic protein binding. Supporting Evidence: PMID:28882996 Sep 7. Fibril structure of amyloid-Ξ²(1-42) by cryo-electron microscopy. |
| GO:0042802 identical protein binding | IPI PMID:17116874 Blocking the apolipoprotein E/amyloid-beta interaction as a ... | ACCEPT | Summary: IPI annotation. APP dimerization (homodimerization) is well-established and functionally relevant for cell adhesion and processing. Reason: APP homodimerization is a core function. More informative than generic protein binding. Supporting Evidence: PMID:17116874 Blocking the apolipoprotein E/amyloid-beta interaction as a potential therapeutic approach for Alzheimer's disease. |
| GO:0042802 identical protein binding | IPI PMID:18059284 Evidence of fibril-like Ξ²-sheet structures in a neurotoxic a... | ACCEPT | Summary: IPI annotation. APP dimerization (homodimerization) is well-established and functionally relevant for cell adhesion and processing. Reason: APP homodimerization is a core function. More informative than generic protein binding. Supporting Evidence: PMID:18059284 Evidence of fibril-like Ξ²-sheet structures in a neurotoxic amyloid intermediate of Alzheimer's Ξ²-amyloid. |
| GO:0042802 identical protein binding | IPI PMID:18483195 Paired beta-sheet structure of an Abeta(1-40) amyloid fibril... | ACCEPT | Summary: IPI annotation. APP dimerization (homodimerization) is well-established and functionally relevant for cell adhesion and processing. Reason: APP homodimerization is a core function. More informative than generic protein binding. Supporting Evidence: PMID:18483195 Paired beta-sheet structure of an Abeta(1-40) amyloid fibril revealed by electron microscopy. |
| GO:0042802 identical protein binding | IPI PMID:18499799 Two-dimensional infrared spectra of isotopically diluted amy... | ACCEPT | Summary: IPI annotation. APP dimerization (homodimerization) is well-established and functionally relevant for cell adhesion and processing. Reason: APP homodimerization is a core function. More informative than generic protein binding. Supporting Evidence: PMID:18499799 Two-dimensional infrared spectra of isotopically diluted amyloid fibrils from Abeta40. |
| GO:0042802 identical protein binding | IPI PMID:19304802 Synaptic transmission block by presynaptic injection of olig... | ACCEPT | Summary: IPI annotation. APP dimerization (homodimerization) is well-established and functionally relevant for cell adhesion and processing. Reason: APP homodimerization is a core function. More informative than generic protein binding. Supporting Evidence: PMID:19304802 Synaptic transmission block by presynaptic injection of oligomeric amyloid beta. |
| GO:0042802 identical protein binding | IPI PMID:19458258 Alpha-helix targeting reduces amyloid-beta peptide toxicity. | ACCEPT | Summary: IPI annotation. APP dimerization (homodimerization) is well-established and functionally relevant for cell adhesion and processing. Reason: APP homodimerization is a core function. More informative than generic protein binding. Supporting Evidence: PMID:19458258 Alpha-helix targeting reduces amyloid-beta peptide toxicity. |
| GO:0042802 identical protein binding | IPI PMID:19706468 Structure-neurotoxicity relationships of amyloid beta-protei... | ACCEPT | Summary: IPI annotation. APP dimerization (homodimerization) is well-established and functionally relevant for cell adhesion and processing. Reason: APP homodimerization is a core function. More informative than generic protein binding. Supporting Evidence: PMID:19706468 Structure-neurotoxicity relationships of amyloid beta-protein oligomers. |
| GO:0042802 identical protein binding | IPI PMID:19706519 Measurement of amyloid fibril mass-per-length by tilted-beam... | ACCEPT | Summary: IPI annotation. APP dimerization (homodimerization) is well-established and functionally relevant for cell adhesion and processing. Reason: APP homodimerization is a core function. More informative than generic protein binding. Supporting Evidence: PMID:19706519 Measurement of amyloid fibril mass-per-length by tilted-beam transmission electron microscopy. |
| GO:0042802 identical protein binding | IPI PMID:19841277 Site-specific modification of Alzheimer's peptides by choles... | ACCEPT | Summary: IPI annotation. APP dimerization (homodimerization) is well-established and functionally relevant for cell adhesion and processing. Reason: APP homodimerization is a core function. More informative than generic protein binding. Supporting Evidence: PMID:19841277 Site-specific modification of Alzheimer's peptides by cholesterol oxidation products enhances aggregation energetics and neurotoxicity. |
| GO:0042802 identical protein binding | IPI PMID:20133839 Mechanism of amyloid plaque formation suggests an intracellu... | ACCEPT | Summary: IPI annotation. APP dimerization (homodimerization) is well-established and functionally relevant for cell adhesion and processing. Reason: APP homodimerization is a core function. More informative than generic protein binding. Supporting Evidence: PMID:20133839 Mechanism of amyloid plaque formation suggests an intracellular basis of Abeta pathogenicity. |
| GO:0042802 identical protein binding | IPI PMID:22036569 Arc/Arg3.1 regulates an endosomal pathway essential for acti... | ACCEPT | Summary: IPI annotation. APP dimerization (homodimerization) is well-established and functionally relevant for cell adhesion and processing. Reason: APP homodimerization is a core function. More informative than generic protein binding. Supporting Evidence: PMID:22036569 Arc/Arg3.1 regulates an endosomal pathway essential for activity-dependent Ξ²-amyloid generation. |
| GO:0042802 identical protein binding | IPI PMID:22179788 The extracellular chaperone clusterin sequesters oligomeric ... | ACCEPT | Summary: Abeta self-associates forming dimers and higher oligomers. Reason: Direct single-molecule fluorescence demonstration of Abeta oligomerization. Supporting Evidence: PMID:22179788 AΞ²(1-40) forms a heterogeneous distribution of small oligomers (from dimers to 50-mers) |
| GO:0042802 identical protein binding | IPI PMID:25543257 Modeling an in-register, parallel "iowa" aΞ² fibril structure... | ACCEPT | Summary: IPI annotation. APP dimerization (homodimerization) is well-established and functionally relevant for cell adhesion and processing. Reason: APP homodimerization is a core function. More informative than generic protein binding. Supporting Evidence: PMID:25543257 Dec 24. Modeling an in-register, parallel "iowa" aΞ² fibril structure using solid-state NMR data from labeled samples with rosetta. |
| GO:0042802 identical protein binding | IPI PMID:30158114 TLR5 decoy receptor as a novel anti-amyloid therapeutic for ... | ACCEPT | Summary: IPI annotation. APP dimerization (homodimerization) is well-established and functionally relevant for cell adhesion and processing. Reason: APP homodimerization is a core function. More informative than generic protein binding. Supporting Evidence: PMID:30158114 TLR5 decoy receptor as a novel anti-amyloid therapeutic for Alzheimer's disease. |
| GO:0005615 extracellular space | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation based on electronic inference. Consistent with APP biology. Reason: IEA annotation consistent with known APP functions. |
| GO:0006816 calcium ion transport | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: IEA annotation for calcium ion transport. APP is not a calcium transporter. Abeta peptides can form calcium-permeable pores in membranes and Abeta oligomers disrupt calcium homeostasis, but APP itself does not transport calcium. This is an indirect effect of cleavage products. Reason: APP is not a calcium transporter. The calcium effects are indirect, mediated by Abeta pore formation and signaling disruption. Over-annotation. |
| GO:0007611 learning or memory | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA annotation for learning or memory. APP and its cleavage products (especially Abeta oligomers) affect learning and memory, but this is a downstream phenotypic consequence of APP processing rather than a core molecular function. Reason: learning or memory is a downstream consequence of APP/Abeta biology. Important for disease relevance but not a core function. Keep as non-core. |
| GO:0010288 response to lead ion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA annotation for response to lead ion. Lead exposure has been shown to increase APP expression and Abeta production, but this is a response to an environmental toxin rather than a core function. Reason: Response to lead ion is an environmental response, not a core function of APP. Keep as non-core. |
| GO:0016504 peptidase activator activity | IEA GO_REF:0000107 | UNDECIDED | Summary: IEA annotation for peptidase activator activity. It is unclear what specific peptidase APP activates. APP is itself a substrate of multiple peptidases (alpha-, beta-, gamma-secretases) but the mechanism of direct peptidase activation is not well characterized. Reason: Unclear molecular basis for peptidase activator activity. APP is a protease substrate, not clearly a protease activator. Needs further evidence. |
| GO:0030424 axon | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation based on electronic inference. Consistent with APP biology. Reason: IEA annotation consistent with known APP functions. |
| GO:0036269 swimming behavior | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: ISS annotation for swimming behavior based on mouse APP knockout/transgenic studies. These behavioral phenotypes reflect pleiotropic downstream effects of APP loss or Abeta overexpression in mice rather than a core molecular function of APP. Reason: Behavioral phenotype (swimming behavior) observed in mouse models. Not a core function of APP but a downstream consequence. Keep as non-core. |
| GO:0043523 regulation of neuron apoptotic process | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation based on electronic inference. Consistent with APP biology. Reason: IEA annotation consistent with known APP functions. |
| GO:0044304 main axon | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation based on electronic inference. Consistent with APP biology. Reason: IEA annotation consistent with known APP functions. |
| GO:0045471 response to ethanol | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation based on electronic inference. Consistent with APP biology. Reason: IEA annotation consistent with known APP functions. |
| GO:0051247 positive regulation of protein metabolic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: IEA annotation for positive regulation of protein metabolic process. Very broad term that does not provide useful information about APP function. Reason: Too broad to be informative. Over-annotation. |
| GO:0070555 response to interleukin-1 | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: IEA annotation to a broad cytokine-response term. APP and its cleavage products can participate in inflammatory contexts, but this label is not specific enough for APP core-function curation. Reason: Response to interleukin-1 is too broad and downstream to be promoted as an informative APP function; more specific processing, trafficking, synaptic, or fragment-specific mechanisms should be used where supported. |
| GO:0070851 growth factor receptor binding | IEA GO_REF:0000107 | UNDECIDED | Summary: IEA annotation for growth factor receptor binding. The specific growth factor receptor that APP binds is unclear. sAPPalpha has growth factor-like properties but the receptor is not well defined. Reason: Unclear which growth factor receptor APP binds. Needs further evidence. |
| GO:0071280 cellular response to copper ion | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation based on electronic inference. Consistent with APP biology. Reason: IEA annotation consistent with known APP functions. |
| GO:0071287 cellular response to manganese ion | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation based on electronic inference. Consistent with APP biology. Reason: IEA annotation consistent with known APP functions. |
| GO:0071320 cellular response to cAMP | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation based on electronic inference. Consistent with APP biology. Reason: IEA annotation consistent with known APP functions. |
| GO:0071874 cellular response to norepinephrine stimulus | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation based on electronic inference. Consistent with APP biology. Reason: IEA annotation consistent with known APP functions. |
| GO:0097449 astrocyte projection | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation based on electronic inference. Consistent with APP biology. Reason: IEA annotation consistent with known APP functions. |
| GO:0098992 neuronal dense core vesicle | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation based on electronic inference. Consistent with APP biology. Reason: IEA annotation consistent with known APP functions. |
| GO:0110088 hippocampal neuron apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA annotation for hippocampal neuron apoptotic process. This is an overly specific term for Abeta-mediated neurotoxicity. The neurotoxic effect of Abeta is well established but this is a pathological consequence, not a core function of APP. Reason: Pathological consequence of Abeta accumulation, not a core function. Overly specific cell-type qualification. Keep as non-core. |
| GO:1990090 cellular response to nerve growth factor stimulus | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation based on electronic inference. Consistent with APP biology. Reason: IEA annotation consistent with known APP functions. |
| GO:1990418 response to insulin-like growth factor stimulus | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation based on electronic inference. Consistent with APP biology. Reason: IEA annotation consistent with known APP functions. |
| GO:1990761 growth cone lamellipodium | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation based on electronic inference. Consistent with APP biology. Reason: IEA annotation consistent with known APP functions. |
| GO:1990812 growth cone filopodium | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation based on electronic inference. Consistent with APP biology. Reason: IEA annotation consistent with known APP functions. |
| GO:0005794 Golgi apparatus | IDA GO_REF:0000052 | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. |
| GO:0005615 extracellular space | NAS P05067-PRO_0000000093 PMID:18568035 Amyloid-beta protein dimers isolated directly from Alzheimer... | ACCEPT | Summary: NAS annotation for Abeta localization in extracellular space. Shankar et al. (2008) extracted soluble Abeta oligomers from AD brain cortex, demonstrating extracellular presence. Reason: Annotation correctly targets Abeta cleavage product (PRO_0000000093) and extracellular localization is supported by extraction from brain tissue. Supporting Evidence: PMID:18568035 We extracted soluble amyloid-beta protein (Abeta) oligomers directly from the cerebral cortex of subjects with Alzheimer's disease. |
| GO:0005886 plasma membrane | NAS P05067-PRO_0000000093 PMID:18568035 Amyloid-beta protein dimers isolated directly from Alzheimer... | ACCEPT | Summary: NAS annotation for Abeta at plasma membrane. Abeta oligomers act at synaptic sites, consistent with membrane association. Reason: Annotation correctly targets Abeta cleavage product. Membrane association implied by synaptic site of action, consistent with other evidence for plasma membrane localization. Supporting Evidence: PMID:18568035 The oligomers potently inhibited long-term potentiation (LTP), enhanced long-term depression (LTD) and reduced dendritic spine density in normal rodent hippocampus. |
| GO:0043408 regulation of MAPK cascade | ISS GO_REF:0000114 | ACCEPT | Summary: ISS annotation based on sequence similarity to characterized ortholog. Reason: ISS annotation consistent with known APP functions. |
| GO:0045666 positive regulation of neuron differentiation | ISS GO_REF:0000114 | ACCEPT | Summary: ISS annotation based on sequence similarity to characterized ortholog. Reason: ISS annotation consistent with known APP functions. |
| GO:1900272 negative regulation of long-term synaptic potentiation | IDA P05067-PRO_0000000093 PMID:18568035 Amyloid-beta protein dimers isolated directly from Alzheimer... | KEEP AS NON CORE | Summary: IDA annotation for Abeta-mediated LTP inhibition. Shankar et al. (2008) demonstrated that Abeta oligomers extracted directly from AD brains potently inhibited LTP in rodent hippocampus. Crucially, this effect was specifically attributable to Abeta DIMERS, not monomers or higher-order aggregates. Reason: Well-supported IDA annotation correctly targeting Abeta cleavage product. This is a real cleavage-product synaptic effect, but it is not a core evolved full-length APP function and should be kept as non-core in this gene-level review. Supporting Evidence: PMID:18568035 The oligomers potently inhibited long-term potentiation (LTP), enhanced long-term depression (LTD) and reduced dendritic spine density in normal rodent hippocampus |
| GO:1900272 negative regulation of long-term synaptic potentiation | NAS PMID:19242475 Cellular prion protein mediates impairment of synaptic plast... | KEEP AS NON CORE | Summary: NAS annotation based on author statement. Reason: NAS annotation is supported by literature, but negative regulation of long-term synaptic potentiation is a cleavage-product/pathophysiological synaptic effect rather than a core evolved APP function. Supporting Evidence: PMID:19242475 Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers. |
| GO:1900454 positive regulation of long-term synaptic depression | IDA P05067-PRO_0000000093 PMID:18568035 Amyloid-beta protein dimers isolated directly from Alzheimer... | ACCEPT | Summary: IDA annotation for Abeta-mediated LTD enhancement. Shankar et al. (2008) showed that Abeta dimers from AD brains enhanced LTD in rodent hippocampus. The mechanism requires metabotropic glutamate receptors (mGluRs). Reason: Well-supported IDA annotation correctly targeting Abeta cleavage product. LTD enhancement is a core synaptotoxic function of Abeta dimers. Supporting Evidence: PMID:18568035 The oligomers potently inhibited long-term potentiation (LTP), enhanced long-term depression (LTD) and reduced dendritic spine density in normal rodent hippocampus |
| GO:1900454 positive regulation of long-term synaptic depression | NAS PMID:19242475 Cellular prion protein mediates impairment of synaptic plast... | ACCEPT | Summary: NAS annotation based on author statement. Reason: NAS annotation supported by literature. Supporting Evidence: PMID:19242475 Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers. |
| GO:1902951 negative regulation of dendritic spine maintenance | IDA P05067-PRO_0000000093 PMID:18568035 Amyloid-beta protein dimers isolated directly from Alzheimer... | ACCEPT | Summary: IDA annotation for Abeta-mediated spine loss. Shankar et al. (2008) showed that Abeta oligomers from AD brains reduced dendritic spine density. Effects specifically attributable to Abeta dimers and require NMDA receptors. Reason: Well-supported IDA annotation correctly targeting Abeta cleavage product. Spine loss is a core synaptotoxic function of Abeta dimers. Supporting Evidence: PMID:18568035 The oligomers potently inhibited long-term potentiation (LTP), enhanced long-term depression (LTD) and reduced dendritic spine density in normal rodent hippocampus |
| GO:1902951 negative regulation of dendritic spine maintenance | NAS PMID:22820466 Alzheimer amyloid-Ξ² oligomer bound to postsynaptic prion pro... | ACCEPT | Summary: NAS annotation based on author statement. Reason: NAS annotation supported by literature. Supporting Evidence: PMID:22820466 Alzheimer amyloid-Ξ² oligomer bound to postsynaptic prion protein activates Fyn to impair neurons. |
| GO:0043525 positive regulation of neuron apoptotic process | IGI PMID:23164821 Clusterin regulates Ξ²-amyloid toxicity via Dickkopf-1-driven... | KEEP AS NON CORE | Summary: IGI annotation for positive regulation of neuron apoptotic process. Abeta and gamma-CTF fragments promote neuronal apoptosis, but this is a pathological consequence of aberrant APP processing rather than a core physiological function. Reason: Neurotoxicity is a pathological consequence of Abeta, not a core APP function. Keep as non-core. Supporting Evidence: PMID:23164821 silencing of DKK1 blocks AΞ² neurotoxicity |
| GO:0032224 positive regulation of synaptic transmission, cholinergic | IDA PMID:33239400 Implications of Oligomeric Amyloid-Beta (oAΞ²(42)) Signaling ... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:33239400 oAΞ²42 activates both homomeric Ξ±7- and heteromeric Ξ±7Ξ²2-nAChR subtypes while preferentially enhancing Ξ±7Ξ²2-nAChR open-dwell times |
| GO:0043083 synaptic cleft | TAS PMID:33239400 Implications of Oligomeric Amyloid-Beta (oAΞ²(42)) Signaling ... | ACCEPT | Summary: TAS annotation based on author statement in referenced publication. Reason: TAS annotation supported by literature. Supporting Evidence: PMID:33239400 the oligomeric form of amyloid-Ξ² (oAΞ²42), interacting with Ξ±7-containing nicotinic acetylcholine receptor (nAChR) subtypes |
| GO:0048018 receptor ligand activity | IDA PMID:33239400 Implications of Oligomeric Amyloid-Beta (oAΞ²(42)) Signaling ... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:33239400 these data provide a molecular mechanism supporting a role for Ξ±7Ξ²2-nAChR in mediating the effects of oAΞ²42 |
| GO:0106003 amyloid-beta complex | IDA PMID:33239400 Implications of Oligomeric Amyloid-Beta (oAΞ²(42)) Signaling ... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:33239400 the oligomeric form of amyloid-Ξ² (oAΞ²42) |
| GO:0031901 early endosome membrane | IDA PMID:16174740 Neuronal sorting protein-related receptor sorLA/LR11 regulat... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:16174740 Neuronal sorting protein-related receptor sorLA/LR11 regulates processing of the amyloid precursor protein. |
| GO:0048018 receptor ligand activity | IDA PMID:16174740 Neuronal sorting protein-related receptor sorLA/LR11 regulat... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:16174740 Neuronal sorting protein-related receptor sorLA/LR11 regulates processing of the amyloid precursor protein. |
| GO:1904646 cellular response to amyloid-beta | IDA PMID:29518356 TREM2 Is a Receptor for Ξ²-Amyloid that Mediates Microglial F... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:29518356 TREM2 Is a Receptor for Ξ²-Amyloid that Mediates Microglial Function. |
| GO:1905606 regulation of presynapse assembly | IMP PMID:19726636 Presynaptic and postsynaptic interaction of the amyloid prec... | ACCEPT | Summary: IMP annotation based on mutant phenotype analysis. Reason: IMP annotation supported by mutant phenotype data. Supporting Evidence: PMID:19726636 Presynaptic and postsynaptic interaction of the amyloid precursor protein promotes peripheral and central synaptogenesis. |
| GO:1905606 regulation of presynapse assembly | IDA PMID:19726636 Presynaptic and postsynaptic interaction of the amyloid prec... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:19726636 Presynaptic and postsynaptic interaction of the amyloid precursor protein promotes peripheral and central synaptogenesis. |
| GO:0030425 dendrite | IDA PMID:24012003 Metabotropic glutamate receptor 5 is a coreceptor for Alzhei... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:24012003 Metabotropic glutamate receptor 5 is a coreceptor for Alzheimer aΞ² oligomer bound to cellular prion protein. |
| GO:0120283 protein serine/threonine kinase binding | IPI PMID:24305806 Pharmacologic inhibition of ROCK2 suppresses amyloid-Ξ² produ... | ACCEPT | Summary: IPI annotation showing specific protein interaction. Reason: IPI annotation with specific molecular function is more informative than generic protein binding. Supporting Evidence: PMID:24305806 Pharmacologic inhibition of ROCK2 suppresses amyloid-Ξ² production in an Alzheimer's disease mouse model. |
| GO:0055096 low-density lipoprotein particle mediated signaling | IDA PMID:26005850 Central role for PICALM in amyloid-Ξ² blood-brain barrier tra... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:26005850 PICALM regulated PICALM/clathrin-dependent internalization of AΞ² bound to the low density lipoprotein receptor related protein-1 |
| GO:0098989 NMDA selective glutamate receptor signaling pathway | TAS PMID:17360908 Natural oligomers of the Alzheimer amyloid-beta protein indu... | ACCEPT | Summary: TAS annotation based on author statement in referenced publication. Reason: TAS annotation supported by literature. Supporting Evidence: PMID:17360908 Natural oligomers of the Alzheimer amyloid-beta protein induce reversible synapse loss by modulating an NMDA-type glutamate receptor-dependent signaling pathway. |
| GO:1902993 positive regulation of amyloid precursor protein catabolic process | IGI PMID:22406537 A multimodal RAGE-specific inhibitor reduces amyloid Ξ²-media... | ACCEPT | Summary: RAGE-mediated Abeta signaling affects APP processing through beta-secretase activity. Reason: Study shows RAGE inhibitor reduced beta-secretase activity and Abeta production. Supporting Evidence: PMID:22406537 In brain, FPS-ZM1 bound exclusively to RAGE, which inhibited Ξ²-secretase activity and AΞ² production and suppressed microglia activation and the neuroinflammatory response |
| GO:0050850 positive regulation of calcium-mediated signaling | IGI PMID:22500019 Amyloid Ξ² (AΞ²) peptide directly activates amylin-3 receptor ... | KEEP AS NON CORE | Summary: IGI annotation for positive regulation of calcium-mediated signaling. Abeta disrupts calcium homeostasis. Downstream pathological effect. Reason: Calcium signaling disruption is a downstream effect of Abeta. Keep as non-core. Supporting Evidence: PMID:22500019 2012 Apr 12. Amyloid Ξ² (AΞ²) peptide directly activates amylin-3 receptor subtype by triggering multiple intracellular signaling pathways. |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-9839072 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9839072 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0010628 positive regulation of gene expression | IMP PMID:15457210 RAGE potentiates Abeta-induced perturbation of neuronal func... | KEEP AS NON CORE | Summary: IMP annotation for positive regulation of gene expression. Gene expression changes are downstream effects of APP processing and Abeta signaling. Some may be mediated by AICD transcriptional regulation (controversial). Not core APP function. Reason: positive regulation of gene expression is a downstream effect. Keep as non-core. Supporting Evidence: PMID:15457210 Double Tgs (mutant APP (mAPP)/RAGE) displayed early abnormalities in spatial learning/memory, accompanied by altered activation of markers of synaptic plasticity and exaggerated neuropathologic findings, before such changes were found in mAPP mice |
| GO:1900272 negative regulation of long-term synaptic potentiation | IGI PMID:15457210 RAGE potentiates Abeta-induced perturbation of neuronal func... | KEEP AS NON CORE | Summary: IGI annotation from RAGE interaction study. Arancio et al. (2004) showed mAPP/RAGE double transgenics have early LTP deficits, but RAGE is the receptor mediating Abeta effects. The annotation is technically valid but the mechanism is RAGE-dependent. Reason: While LTP inhibition occurs in mAPP transgenics, this paper demonstrates it is RAGE-mediated. Keep as non-core because it reflects Abeta/RAGE-dependent synaptic physiology rather than the defining full-length APP function. Supporting Evidence: PMID:15457210 RAGE is a cofactor for Abeta-induced neuronal perturbation in a model of Alzheimer's-type pathology |
| GO:1901224 positive regulation of non-canonical NF-kappaB signal transduction | IGI PMID:15457210 RAGE potentiates Abeta-induced perturbation of neuronal func... | KEEP AS NON CORE | Summary: IGI annotation for positive regulation of non-canonical NF-kappaB signal transduction. Abeta-mediated inflammatory signaling. Downstream effect. Reason: NF-kappaB activation is a downstream inflammatory effect of Abeta. Keep as non-core. Supporting Evidence: PMID:15457210 Receptor for Advanced Glycation Endproducts (RAGE), a multiligand receptor in the immunoglobulin superfamily, functions as a signal-transducing cell surface acceptor for amyloid-beta peptide (Abeta) |
| GO:2000406 positive regulation of T cell migration | IMP PMID:19660551 Biochemical and immunohistochemical analysis of an Alzheimer... | KEEP AS NON CORE | Summary: IMP annotation for positive regulation of T cell migration. These immune/inflammatory effects are primarily mediated by Abeta cleavage products activating innate immune cells (microglia, astrocytes) rather than representing core functions of full-length APP. Reason: Immune/inflammatory annotation (positive regulation of T cell migration) reflects downstream Abeta-mediated effects. Not a core function of APP itself. Keep as non-core. Supporting Evidence: PMID:19660551 2009 Aug 4. Biochemical and immunohistochemical analysis of an Alzheimer's disease mouse model reveals the presence of multiple cerebral Abeta assembly forms throughout life. |
| GO:0007611 learning or memory | IGI PMID:20164328 Loss of alpha7 nicotinic receptors enhances beta-amyloid oli... | KEEP AS NON CORE | Summary: IGI annotation for learning or memory. APP and its cleavage products (especially Abeta oligomers) affect learning and memory, but this is a downstream phenotypic consequence of APP processing rather than a core molecular function. Reason: learning or memory is a downstream consequence of APP/Abeta biology. Important for disease relevance but not a core function. Keep as non-core. Supporting Evidence: PMID:20164328 Loss of alpha7 nicotinic receptors enhances beta-amyloid oligomer accumulation, exacerbating early-stage cognitive decline and septohippocampal pathology in a mouse model of Alzheimer's disease. |
| GO:0010468 regulation of gene expression | IGI PMID:21857966 WNT5A signaling contributes to AΞ²-induced neuroinflammation ... | KEEP AS NON CORE | Summary: IGI annotation for regulation of gene expression. Gene expression changes are downstream effects of APP processing and Abeta signaling. Some may be mediated by AICD transcriptional regulation (controversial). Not core APP function. Reason: regulation of gene expression is a downstream effect. Keep as non-core. Supporting Evidence: PMID:21857966 WNT5A signaling contributes to AΞ²-induced neuroinflammation and neurotoxicity. |
| GO:0030111 regulation of Wnt signaling pathway | IC PMID:21857966 WNT5A signaling contributes to AΞ²-induced neuroinflammation ... | KEEP AS NON CORE | Summary: IC annotation for regulation of Wnt signaling pathway. APP has been reported to interact with Wnt pathway components. Not a core function. Reason: Wnt signaling regulation is not a core function of APP. Keep as non-core. Supporting Evidence: PMID:21857966 WNT5A signaling contributes to AΞ²-induced neuroinflammation and neurotoxicity. |
| GO:0046330 positive regulation of JNK cascade | IGI PMID:23921129 FcΞ³RIIb mediates amyloid-Ξ² neurotoxicity and memory impairme... | KEEP AS NON CORE | Summary: IGI annotation for positive regulation of JNK cascade. APP cytoplasmic domain interacts with JIP1 and can activate JNK signaling. Downstream signaling effect. Reason: JNK cascade activation is a downstream signaling effect. Keep as non-core. Supporting Evidence: PMID:23921129 Neuronal FcΞ³RIIb activated ER stress and caspase-12 |
| GO:0048169 regulation of long-term neuronal synaptic plasticity | IGI PMID:23921129 FcΞ³RIIb mediates amyloid-Ξ² neurotoxicity and memory impairme... | KEEP AS NON CORE | Summary: IGI annotation based on genetic interaction evidence. NOTE: Many IGI annotations for APP involve Abeta-specific effects from transgenic mouse studies and may not represent full-length APP function. Reason: IGI annotation is supported by genetic interaction data, but negative regulation of long-term synaptic potentiation is a cleavage-product or transgenic model output rather than a core evolved full-length APP function. Supporting Evidence: PMID:23921129 Fcgr2b deficiency ameliorated AΞ²-induced inhibition of long-term potentiation |
| GO:0007611 learning or memory | IGI PMID:20445063 Memory impairment in transgenic Alzheimer mice requires cell... | KEEP AS NON CORE | Summary: IGI annotation for learning or memory. APP and its cleavage products (especially Abeta oligomers) affect learning and memory, but this is a downstream phenotypic consequence of APP processing rather than a core molecular function. Reason: learning or memory is a downstream consequence of APP/Abeta biology. Important for disease relevance but not a core function. Keep as non-core. Supporting Evidence: PMID:20445063 Memory impairment in transgenic Alzheimer mice requires cellular prion protein. |
| GO:0007611 learning or memory | IGI PMID:24012003 Metabotropic glutamate receptor 5 is a coreceptor for Alzhei... | KEEP AS NON CORE | Summary: IGI annotation for learning or memory. APP and its cleavage products (especially Abeta oligomers) affect learning and memory, but this is a downstream phenotypic consequence of APP processing rather than a core molecular function. Reason: learning or memory is a downstream consequence of APP/Abeta biology. Important for disease relevance but not a core function. Keep as non-core. Supporting Evidence: PMID:24012003 Metabotropic glutamate receptor 5 is a coreceptor for Alzheimer aΞ² oligomer bound to cellular prion protein. |
| GO:0010628 positive regulation of gene expression | IGI PMID:28008308 The Protective Role of microRNA-200c in Alzheimer's Disease ... | KEEP AS NON CORE | Summary: IGI annotation for positive regulation of gene expression. Gene expression changes are downstream effects of APP processing and Abeta signaling. Some may be mediated by AICD transcriptional regulation (controversial). Not core APP function. Reason: positive regulation of gene expression is a downstream effect. Keep as non-core. Supporting Evidence: PMID:28008308 eCollection 2016. The Protective Role of microRNA-200c in Alzheimer's Disease Pathologies Is Induced by Beta Amyloid-Triggered Endoplasmic Reticulum Stress. |
| GO:0010629 negative regulation of gene expression | IGI PMID:28008308 The Protective Role of microRNA-200c in Alzheimer's Disease ... | KEEP AS NON CORE | Summary: IGI annotation for negative regulation of gene expression. Gene expression changes are downstream effects of APP processing and Abeta signaling. Some may be mediated by AICD transcriptional regulation (controversial). Not core APP function. Reason: negative regulation of gene expression is a downstream effect. Keep as non-core. Supporting Evidence: PMID:28008308 eCollection 2016. The Protective Role of microRNA-200c in Alzheimer's Disease Pathologies Is Induced by Beta Amyloid-Triggered Endoplasmic Reticulum Stress. |
| GO:0046982 protein heterodimerization activity | IPI PMID:19660551 Biochemical and immunohistochemical analysis of an Alzheimer... | ACCEPT | Summary: Abeta forms SDS-stable dimers in J20 transgenic mouse brain. Reason: Direct biochemical demonstration of Abeta dimerization. Supporting Evidence: PMID:19660551 Using an immunoprecipitation/Western blotting technique we find an age-dependent increase in Abeta monomer and SDS-stable dimer |
| GO:0050808 synapse organization | IGI PMID:24012003 Metabotropic glutamate receptor 5 is a coreceptor for Alzhei... | ACCEPT | Summary: IGI annotation based on genetic interaction evidence. NOTE: Many IGI annotations for APP involve Abeta-specific effects from transgenic mouse studies and may not represent full-length APP function. Reason: IGI annotation supported by genetic interaction data. Note potential cleavage product specificity. Supporting Evidence: PMID:24012003 Metabotropic glutamate receptor 5 is a coreceptor for Alzheimer aΞ² oligomer bound to cellular prion protein. |
| GO:0051247 positive regulation of protein metabolic process | IMP PMID:11404397 Beta-amyloid activates the mitogen-activated protein kinase ... | MARK AS OVER ANNOTATED | Summary: IMP annotation based on mutant phenotype analysis, but the GO term is broad and does not identify the specific APP or amyloid-beta-dependent signaling/protein-metabolism target. Reason: The evidence may support a downstream effect on protein metabolism, but GO:0051247 is too broad for informative APP curation and should not be promoted as a core function. Supporting Evidence: PMID:11404397 Beta-amyloid activates the mitogen-activated protein kinase cascade via hippocampal alpha7 nicotinic acetylcholine receptors: In vitro and in vivo mechanisms related to Alzheimer's disease. |
| GO:0051262 protein tetramerization | IPI PMID:19660551 Biochemical and immunohistochemical analysis of an Alzheimer... | ACCEPT | Summary: Abeta forms multiple assembly forms including oligomers in J20 mouse brain. Reason: Study shows multiple Abeta assembly forms detected biochemically. Supporting Evidence: PMID:19660551 These data demonstrate the presence of multiple assembly forms of Abeta throughout the life of J20 mice |
| GO:0070206 protein trimerization | IPI PMID:19660551 Biochemical and immunohistochemical analysis of an Alzheimer... | ACCEPT | Summary: Abeta forms multiple oligomeric assembly forms in J20 mouse brain. Reason: Study demonstrates multiple Abeta assembly forms including oligomers. Supporting Evidence: PMID:19660551 These data demonstrate the presence of multiple assembly forms of Abeta throughout the life of J20 mice |
| GO:0150003 regulation of spontaneous synaptic transmission | IGI PMID:15457210 RAGE potentiates Abeta-induced perturbation of neuronal func... | ACCEPT | Summary: Abeta-RAGE interaction affects synaptic plasticity markers in transgenic mouse models. Reason: Study shows RAGE-mediated Abeta effects on synaptic function. Supporting Evidence: PMID:15457210 Double Tgs (mutant APP (mAPP)/RAGE) displayed early abnormalities in spatial learning/memory, accompanied by altered activation of markers of synaptic plasticity and exaggerated neuropathologic findings, before such changes were found in mAPP mice |
| GO:1905908 positive regulation of amyloid fibril formation | IMP PMID:19660551 Biochemical and immunohistochemical analysis of an Alzheimer... | KEEP AS NON CORE | Summary: IMP annotation for positive regulation of amyloid fibril formation. While amyloid fibril formation is central to AD pathology, it is a pathological process rather than a core physiological function. Reason: Amyloid fibril formation is pathological rather than a core physiological function. Keep as non-core. Supporting Evidence: PMID:19660551 biochemical fractionation and ELISA analysis revealed evidence of TBS and triton-insoluble sedimentable Abeta aggregates at the earliest ages studied |
| GO:0034361 very-low-density lipoprotein particle | IPI PMID:9211985 Association of human, rat, and rabbit apolipoprotein E with ... | ACCEPT | Summary: IPI annotation showing specific protein interaction. Reason: IPI annotation with specific molecular function is more informative than generic protein binding. Supporting Evidence: PMID:9211985 when equivalent amounts of apoE3 or E4 were incubated with beta-amyloid (A beta), apoE3 formed 20 times as much SDS-stable complex with the peptide as apoE4 |
| GO:0034362 low-density lipoprotein particle | IPI PMID:9211985 Association of human, rat, and rabbit apolipoprotein E with ... | ACCEPT | Summary: IPI annotation showing specific protein interaction. Reason: IPI annotation with specific molecular function is more informative than generic protein binding. Supporting Evidence: PMID:9211985 Lipoproteins isolated from the plasma of individuals homozygous for either epsilon2 or epsilon3 were incubated with A beta(1-40) |
| GO:0034363 intermediate-density lipoprotein particle | IPI PMID:9211985 Association of human, rat, and rabbit apolipoprotein E with ... | ACCEPT | Summary: IPI annotation showing specific protein interaction. Reason: IPI annotation with specific molecular function is more informative than generic protein binding. Supporting Evidence: PMID:9211985 lipoprotein-associated rabbit apoE (Cys112, Arg158) did bind the peptide |
| GO:0034364 high-density lipoprotein particle | IPI PMID:9211985 Association of human, rat, and rabbit apolipoprotein E with ... | ACCEPT | Summary: IPI annotation showing specific protein interaction. Reason: IPI annotation with specific molecular function is more informative than generic protein binding. Supporting Evidence: PMID:9211985 ApoE2:A beta complex formation was comparable to apoE3:A beta in both native and purified preparations of apoE |
| GO:0042803 protein homodimerization activity | IPI PMID:15447668 MAPK recruitment by beta-amyloid in organotypic hippocampal ... | ACCEPT | Summary: IPI annotation showing specific protein interaction. Reason: IPI annotation with specific molecular function is more informative than generic protein binding. Supporting Evidence: PMID:15447668 MAPK recruitment by beta-amyloid in organotypic hippocampal slice cultures depends on physical state and exposure time. |
| GO:0042803 protein homodimerization activity | IPI PMID:22179788 The extracellular chaperone clusterin sequesters oligomeric ... | ACCEPT | Summary: Abeta forms dimers as part of its oligomerization pathway. Reason: Single-molecule fluorescence shows Abeta forms dimers to 50-mers. Supporting Evidence: PMID:22179788 AΞ²(1-40) forms a heterogeneous distribution of small oligomers (from dimers to 50-mers) |
| GO:0051260 protein homooligomerization | IPI PMID:15447668 MAPK recruitment by beta-amyloid in organotypic hippocampal ... | ACCEPT | Summary: IPI annotation showing specific protein interaction. Reason: IPI annotation with specific molecular function is more informative than generic protein binding. Supporting Evidence: PMID:15447668 MAPK recruitment by beta-amyloid in organotypic hippocampal slice cultures depends on physical state and exposure time. |
| GO:0051260 protein homooligomerization | IPI PMID:18602473 Aggregation and catabolism of disease-associated intra-Abeta... | ACCEPT | Summary: IPI annotation showing specific protein interaction. Reason: IPI annotation with specific molecular function is more informative than generic protein binding. Supporting Evidence: PMID:18602473 2008 Jun 17. Aggregation and catabolism of disease-associated intra-Abeta mutations: reduced proteolysis of AbetaA21G by neprilysin. |
| GO:0051260 protein homooligomerization | IPI PMID:22179788 The extracellular chaperone clusterin sequesters oligomeric ... | ACCEPT | Summary: Abeta self-associates forming a range of oligomeric species from dimers to 50-mers. Reason: Direct single-molecule fluorescence characterization of Abeta oligomerization. Supporting Evidence: PMID:22179788 AΞ²(1-40) forms a heterogeneous distribution of small oligomers (from dimers to 50-mers) |
| GO:0010628 positive regulation of gene expression | IGI PMID:23164821 Clusterin regulates Ξ²-amyloid toxicity via Dickkopf-1-driven... | KEEP AS NON CORE | Summary: IGI annotation for positive regulation of gene expression. Gene expression changes are downstream effects of APP processing and Abeta signaling. Some may be mediated by AICD transcriptional regulation (controversial). Not core APP function. Reason: positive regulation of gene expression is a downstream effect. Keep as non-core. Supporting Evidence: PMID:23164821 AΞ² induces the neuronal expression of the canonical wnt antagonist, Dickkopf-1 (Dkk1) |
| GO:1904591 positive regulation of protein import | IDA PMID:23164821 Clusterin regulates Ξ²-amyloid toxicity via Dickkopf-1-driven... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:23164821 We demonstrate that AΞ² rapidly targets the clusterin protein, causing its intracellular accumulation possibly by blocking its exit from neurons |
| GO:1990000 amyloid fibril formation | EXP PMID:26138908 High-resolution NMR characterization of low abundance oligom... | ACCEPT | Summary: EXP annotation based on experimental evidence. Reason: EXP annotation supported by direct experimental data. Supporting Evidence: PMID:26138908 High-resolution NMR characterization of low abundance oligomers of amyloid-Ξ² without purification. |
| GO:1990000 amyloid fibril formation | EXP PMID:9737846 Solution structure of methionine-oxidized amyloid beta-pepti... | ACCEPT | Summary: EXP annotation based on experimental evidence. Reason: EXP annotation supported by direct experimental data. Supporting Evidence: PMID:9737846 Solution structure of methionine-oxidized amyloid beta-peptide (1-40). |
| GO:0007611 learning or memory | IMP PMID:11880515 The relationship between Abeta and memory in the Tg2576 mous... | KEEP AS NON CORE | Summary: IMP annotation for learning or memory. APP and its cleavage products (especially Abeta oligomers) affect learning and memory, but this is a downstream phenotypic consequence of APP processing rather than a core molecular function. Reason: learning or memory is a downstream consequence of APP/Abeta biology. Important for disease relevance but not a core function. Keep as non-core. Supporting Evidence: PMID:11880515 The relationship between Abeta and memory in the Tg2576 mouse model of Alzheimer's disease. |
| GO:0007612 learning | IMP PMID:11140684 A learning deficit related to age and beta-amyloid plaques i... | KEEP AS NON CORE | Summary: IMP annotation for learning. APP and its cleavage products (especially Abeta oligomers) affect learning and memory, but this is a downstream phenotypic consequence of APP processing rather than a core molecular function. Reason: learning is a downstream consequence of APP/Abeta biology. Important for disease relevance but not a core function. Keep as non-core. Supporting Evidence: PMID:11140684 A learning deficit related to age and beta-amyloid plaques in a mouse model of Alzheimer's disease. |
| GO:0005515 protein binding | IPI PMID:14527950 Generation of the beta-amyloid peptide and the amyloid precu... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:14527950 2003 Oct 3. Generation of the beta-amyloid peptide and the amyloid precursor protein C-terminal fragment gamma are potentiated by FE65L1. |
| GO:0005769 early endosome | IDA PMID:14527950 Generation of the beta-amyloid peptide and the amyloid precu... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:14527950 2003 Oct 3. Generation of the beta-amyloid peptide and the amyloid precursor protein C-terminal fragment gamma are potentiated by FE65L1. |
| GO:0005783 endoplasmic reticulum | IDA PMID:14527950 Generation of the beta-amyloid peptide and the amyloid precu... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:14527950 2003 Oct 3. Generation of the beta-amyloid peptide and the amyloid precursor protein C-terminal fragment gamma are potentiated by FE65L1. |
| GO:0005794 Golgi apparatus | IDA PMID:14527950 Generation of the beta-amyloid peptide and the amyloid precu... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:14527950 2003 Oct 3. Generation of the beta-amyloid peptide and the amyloid precursor protein C-terminal fragment gamma are potentiated by FE65L1. |
| GO:0005615 extracellular space | IDA PMID:29518356 TREM2 Is a Receptor for Ξ²-Amyloid that Mediates Microglial F... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:29518356 TREM2 Is a Receptor for Ξ²-Amyloid that Mediates Microglial Function. |
| GO:0048018 receptor ligand activity | IDA PMID:29518356 TREM2 Is a Receptor for Ξ²-Amyloid that Mediates Microglial F... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:29518356 TREM2 Is a Receptor for Ξ²-Amyloid that Mediates Microglial Function. |
| GO:0014005 microglia development | IGI PMID:22198949 TLR2 is a primary receptor for Alzheimer's amyloid Ξ² peptide... | KEEP AS NON CORE | Summary: IGI annotation for microglia development. These immune/inflammatory effects are primarily mediated by Abeta cleavage products activating innate immune cells (microglia, astrocytes) rather than representing core functions of full-length APP. Reason: Immune/inflammatory annotation (microglia development) reflects downstream Abeta-mediated effects. Not a core function of APP itself. Keep as non-core. Supporting Evidence: PMID:22198949 Microglia activated by extracellularly deposited amyloid Ξ² peptide (AΞ²) act as a two-edged sword in Alzheimer's disease pathogenesis |
| GO:0032760 positive regulation of tumor necrosis factor production | IGI PMID:22198949 TLR2 is a primary receptor for Alzheimer's amyloid Ξ² peptide... | KEEP AS NON CORE | Summary: IGI annotation for positive regulation of tumor necrosis factor production. These immune/inflammatory effects are primarily mediated by Abeta cleavage products activating innate immune cells (microglia, astrocytes) rather than representing core functions of full-length APP. Reason: Immune/inflammatory annotation (positive regulation of tumor necrosis factor production) reflects downstream Abeta-mediated effects. Not a core function of APP itself. Keep as non-core. Supporting Evidence: PMID:22198949 they damage neurons by releasing neurotoxic proinflammatory mediators (M1 activation) |
| GO:0005515 protein binding | IPI PMID:12054541 A secreted form of human ADAM9 has an alpha-secretase activi... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:12054541 A secreted form of human ADAM9 has an alpha-secretase activity for APP. |
| GO:0005515 protein binding | IPI PMID:9774383 Evidence that tumor necrosis factor alpha converting enzyme ... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:9774383 Evidence that tumor necrosis factor alpha converting enzyme is involved in regulated alpha-secretase cleavage of the Alzheimer amyloid protein precursor. |
| GO:0019899 enzyme binding | IPI PMID:17112471 ADAM19 is tightly associated with constitutive Alzheimer's d... | ACCEPT | Summary: IPI annotation showing specific protein interaction. Reason: IPI annotation with specific molecular function is more informative than generic protein binding. Supporting Evidence: PMID:17112471 ADAM19 is tightly associated with constitutive Alzheimer's disease APP alpha-secretase in A172 cells. |
| GO:0050729 positive regulation of inflammatory response | IMP PMID:29961672 miR-15b reduces amyloid-Ξ² accumulation in SH-SY5Y cell line ... | KEEP AS NON CORE | Summary: IMP annotation for positive regulation of inflammatory response. These immune/inflammatory effects are primarily mediated by Abeta cleavage products activating innate immune cells (microglia, astrocytes) rather than representing core functions of full-length APP. Reason: Immune/inflammatory annotation (positive regulation of inflammatory response) reflects downstream Abeta-mediated effects. Not a core function of APP itself. Keep as non-core. Supporting Evidence: PMID:29961672 2018 Dec 21. miR-15b reduces amyloid-Ξ² accumulation in SH-SY5Y cell line through targetting NF-ΞΊB signaling and BACE1. |
| GO:1901224 positive regulation of non-canonical NF-kappaB signal transduction | IMP PMID:29961672 miR-15b reduces amyloid-Ξ² accumulation in SH-SY5Y cell line ... | KEEP AS NON CORE | Summary: IMP annotation for positive regulation of non-canonical NF-kappaB signal transduction. Abeta-mediated inflammatory signaling. Downstream effect. Reason: NF-kappaB activation is a downstream inflammatory effect of Abeta. Keep as non-core. Supporting Evidence: PMID:29961672 2018 Dec 21. miR-15b reduces amyloid-Ξ² accumulation in SH-SY5Y cell line through targetting NF-ΞΊB signaling and BACE1. |
| GO:0010468 regulation of gene expression | IMP PMID:29274751 Reduced expression of Na(+)/Ca(2+) exchangers is associated ... | KEEP AS NON CORE | Summary: IMP annotation for regulation of gene expression. Gene expression changes are downstream effects of APP processing and Abeta signaling. Some may be mediated by AICD transcriptional regulation (controversial). Not core APP function. Reason: regulation of gene expression is a downstream effect. Keep as non-core. Supporting Evidence: PMID:29274751 Reduced expression of Na(+)/Ca(2+) exchangers is associated with cognitive deficits seen in Alzheimer's disease model mice. |
| GO:0005515 protein binding | IPI PMID:23973487 Two Ξ²-strands of RAGE participate in the recognition and tra... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:23973487 Two Ξ²-strands of RAGE participate in the recognition and transport of amyloid-Ξ² peptide across the blood brain barrier. |
| GO:0010468 regulation of gene expression | IGI PMID:26200696 Dual pathways mediate Ξ²-amyloid stimulated glutathione relea... | KEEP AS NON CORE | Summary: IGI annotation for regulation of gene expression. Gene expression changes are downstream effects of APP processing and Abeta signaling. Some may be mediated by AICD transcriptional regulation (controversial). Not core APP function. Reason: regulation of gene expression is a downstream effect. Keep as non-core. Supporting Evidence: PMID:26200696 Dual pathways mediate Ξ²-amyloid stimulated glutathione release from astrocytes. |
| GO:0010628 positive regulation of gene expression | IDA PMID:26006083 The multidrug resistance pump ABCB1 is a substrate for the u... | KEEP AS NON CORE | Summary: IDA annotation for positive regulation of gene expression. Gene expression changes are downstream effects of APP processing and Abeta signaling. Some may be mediated by AICD transcriptional regulation (controversial). Not core APP function. Reason: positive regulation of gene expression is a downstream effect. Keep as non-core. Supporting Evidence: PMID:26006083 2015 May 26. The multidrug resistance pump ABCB1 is a substrate for the ubiquitin ligase NEDD4-1. |
| GO:0010629 negative regulation of gene expression | IDA PMID:26006083 The multidrug resistance pump ABCB1 is a substrate for the u... | KEEP AS NON CORE | Summary: IDA annotation for negative regulation of gene expression. Gene expression changes are downstream effects of APP processing and Abeta signaling. Some may be mediated by AICD transcriptional regulation (controversial). Not core APP function. Reason: negative regulation of gene expression is a downstream effect. Keep as non-core. Supporting Evidence: PMID:26006083 2015 May 26. The multidrug resistance pump ABCB1 is a substrate for the ubiquitin ligase NEDD4-1. |
| GO:0106003 amyloid-beta complex | TAS PMID:22500019 Amyloid Ξ² (AΞ²) peptide directly activates amylin-3 receptor ... | ACCEPT | Summary: TAS annotation based on author statement in referenced publication. Reason: TAS annotation supported by literature. Supporting Evidence: PMID:22500019 2012 Apr 12. Amyloid Ξ² (AΞ²) peptide directly activates amylin-3 receptor subtype by triggering multiple intracellular signaling pathways. |
| GO:0005886 plasma membrane | IDA PMID:28164773 Apolipoprotein E-mediated Modulation of ADAM10 in Alzheimer'... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:28164773 Apolipoprotein E-mediated Modulation of ADAM10 in Alzheimer's Disease. |
| GO:0001774 microglial cell activation | IGI PMID:15457210 RAGE potentiates Abeta-induced perturbation of neuronal func... | KEEP AS NON CORE | Summary: IGI annotation for microglial cell activation. These immune/inflammatory effects are primarily mediated by Abeta cleavage products activating innate immune cells (microglia, astrocytes) rather than representing core functions of full-length APP. Reason: Immune/inflammatory annotation (microglial cell activation) reflects downstream Abeta-mediated effects. Not a core function of APP itself. Keep as non-core. Supporting Evidence: PMID:15457210 RAGE is a cofactor for Abeta-induced neuronal perturbation in a model of Alzheimer's-type pathology |
| GO:0001774 microglial cell activation | IGI PMID:22406537 A multimodal RAGE-specific inhibitor reduces amyloid Ξ²-media... | KEEP AS NON CORE | Summary: IGI annotation for microglial cell activation. These immune/inflammatory effects are primarily mediated by Abeta cleavage products activating innate immune cells (microglia, astrocytes) rather than representing core functions of full-length APP. Reason: Immune/inflammatory annotation (microglial cell activation) reflects downstream Abeta-mediated effects. Not a core function of APP itself. Keep as non-core. Supporting Evidence: PMID:22406537 A multimodal RAGE-specific inhibitor reduces amyloid Ξ²-mediated brain disorder in a mouse model of Alzheimer disease. |
| GO:0048143 astrocyte activation | IGI PMID:15457210 RAGE potentiates Abeta-induced perturbation of neuronal func... | KEEP AS NON CORE | Summary: IGI annotation for astrocyte activation. These immune/inflammatory effects are primarily mediated by Abeta cleavage products activating innate immune cells (microglia, astrocytes) rather than representing core functions of full-length APP. Reason: Immune/inflammatory annotation (astrocyte activation) reflects downstream Abeta-mediated effects. Not a core function of APP itself. Keep as non-core. Supporting Evidence: PMID:15457210 RAGE is a cofactor for Abeta-induced neuronal perturbation in a model of Alzheimer's-type pathology |
| GO:0032729 positive regulation of type II interferon production | IGI PMID:17255335 Interferon-gamma and tumor necrosis factor-alpha regulate am... | KEEP AS NON CORE | Summary: IGI annotation for positive regulation of type II interferon production. These immune/inflammatory effects are primarily mediated by Abeta cleavage products activating innate immune cells (microglia, astrocytes) rather than representing core functions of full-length APP. Reason: Immune/inflammatory annotation (positive regulation of type II interferon production) reflects downstream Abeta-mediated effects. Not a core function of APP itself. Keep as non-core. Supporting Evidence: PMID:17255335 Interferon-gamma and tumor necrosis factor-alpha regulate amyloid-beta plaque deposition and beta-secretase expression in Swedish mutant APP transgenic mice. |
| GO:0005886 plasma membrane | IDA PMID:28855300 An Alzheimer-associated TREM2 variant occurs at the ADAM cle... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:28855300 An Alzheimer-associated TREM2 variant occurs at the ADAM cleavage site and affects shedding and phagocytic function. |
| GO:0010628 positive regulation of gene expression | IGI PMID:29061364 Inflammatory microglia are glycolytic and iron retentive and... | KEEP AS NON CORE | Summary: IGI annotation for positive regulation of gene expression. Gene expression changes are downstream effects of APP processing and Abeta signaling. Some may be mediated by AICD transcriptional regulation (controversial). Not core APP function. Reason: positive regulation of gene expression is a downstream effect. Keep as non-core. Supporting Evidence: PMID:29061364 genotype-related increases in glycolysis, accompanied by increased PFKFB3, and an increase in the expression of ferritin |
| GO:0010629 negative regulation of gene expression | IGI PMID:29061364 Inflammatory microglia are glycolytic and iron retentive and... | KEEP AS NON CORE | Summary: IGI annotation for negative regulation of gene expression. Gene expression changes are downstream effects of APP processing and Abeta signaling. Some may be mediated by AICD transcriptional regulation (controversial). Not core APP function. Reason: negative regulation of gene expression is a downstream effect. Keep as non-core. Supporting Evidence: PMID:29061364 microglia prepared from wildtype mice and from transgenic mice that overexpress amyloid precursor protein (APP) and presenilin 1 (PS1; APP/PS1) |
| GO:0032760 positive regulation of tumor necrosis factor production | IGI PMID:29061364 Inflammatory microglia are glycolytic and iron retentive and... | KEEP AS NON CORE | Summary: IGI annotation for positive regulation of tumor necrosis factor production. These immune/inflammatory effects are primarily mediated by Abeta cleavage products activating innate immune cells (microglia, astrocytes) rather than representing core functions of full-length APP. Reason: Immune/inflammatory annotation (positive regulation of tumor necrosis factor production) reflects downstream Abeta-mediated effects. Not a core function of APP itself. Keep as non-core. Supporting Evidence: PMID:29061364 retention of iron in microglia increased TNFΞ± expression |
| GO:0045821 positive regulation of glycolytic process | IGI PMID:29061364 Inflammatory microglia are glycolytic and iron retentive and... | KEEP AS NON CORE | Summary: IGI annotation for positive regulation of glycolytic process. Abeta-mediated metabolic effects in cells. Not a core function of APP. Reason: Metabolic effects downstream of Abeta. Not core APP function. Keep as non-core. Supporting Evidence: PMID:29061364 increases in tumor necrosis factor-Ξ± (TNFΞ±) and nitric oxide synthase 2 (NOS2) were accompanied by increased glycolysis |
| GO:0070555 response to interleukin-1 | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS annotation based on sequence similarity to characterized ortholog, but the GO term is too broad to identify APP-specific biology. Reason: The inferred biology should be represented with more specific APP processing, trafficking, synaptic, inflammatory, or fragment-specific regulatory terms rather than this broad cytokine-response term. |
| GO:0005515 protein binding | IPI PMID:28720718 Phosphorylation of amyloid precursor protein by mutant LRRK2... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:28720718 Phosphorylation of amyloid precursor protein by mutant LRRK2 promotes AICD activity and neurotoxicity in Parkinson's disease. |
| GO:1900272 negative regulation of long-term synaptic potentiation | IGI PMID:16636059 Neprilysin-sensitive synapse-associated amyloid-beta peptide... | KEEP AS NON CORE | Summary: IGI annotation based on genetic interaction evidence. NOTE: Many IGI annotations for APP involve Abeta-specific effects from transgenic mouse studies and may not represent full-length APP function. Reason: IGI annotation supported by genetic interaction data, but the phenotype reflects neprilysin-sensitive amyloid-beta oligomer effects on plasticity rather than the core evolved function of full-length APP. Supporting Evidence: PMID:16636059 2006 Apr 24. Neprilysin-sensitive synapse-associated amyloid-beta peptide oligomers impair neuronal plasticity and cognitive function. |
| GO:0032722 positive regulation of chemokine production | IGI PMID:22406537 A multimodal RAGE-specific inhibitor reduces amyloid Ξ²-media... | KEEP AS NON CORE | Summary: IGI annotation for positive regulation of chemokine production. These immune/inflammatory effects are primarily mediated by Abeta cleavage products activating innate immune cells (microglia, astrocytes) rather than representing core functions of full-length APP. Reason: Immune/inflammatory annotation (positive regulation of chemokine production) reflects downstream Abeta-mediated effects. Not a core function of APP itself. Keep as non-core. Supporting Evidence: PMID:22406537 In brain, FPS-ZM1 bound exclusively to RAGE, which inhibited Ξ²-secretase activity and AΞ² production and suppressed microglia activation and the neuroinflammatory response |
| GO:0032731 positive regulation of interleukin-1 beta production | IGI PMID:22406537 A multimodal RAGE-specific inhibitor reduces amyloid Ξ²-media... | KEEP AS NON CORE | Summary: IGI annotation for positive regulation of interleukin-1 beta production. These immune/inflammatory effects are primarily mediated by Abeta cleavage products activating innate immune cells (microglia, astrocytes) rather than representing core functions of full-length APP. Reason: Immune/inflammatory annotation (positive regulation of interleukin-1 beta production) reflects downstream Abeta-mediated effects. Not a core function of APP itself. Keep as non-core. Supporting Evidence: PMID:22406537 Receptor for advanced glycation end products (RAGE) mediates AΞ²-induced perturbations in cerebral vessels, neurons, and microglia in AD |
| GO:0032755 positive regulation of interleukin-6 production | IGI PMID:22406537 A multimodal RAGE-specific inhibitor reduces amyloid Ξ²-media... | KEEP AS NON CORE | Summary: IGI annotation for positive regulation of interleukin-6 production. These immune/inflammatory effects are primarily mediated by Abeta cleavage products activating innate immune cells (microglia, astrocytes) rather than representing core functions of full-length APP. Reason: Immune/inflammatory annotation (positive regulation of interleukin-6 production) reflects downstream Abeta-mediated effects. Not a core function of APP itself. Keep as non-core. Supporting Evidence: PMID:22406537 Receptor for advanced glycation end products (RAGE) mediates AΞ²-induced perturbations in cerebral vessels, neurons, and microglia in AD |
| GO:0032760 positive regulation of tumor necrosis factor production | IGI PMID:22406537 A multimodal RAGE-specific inhibitor reduces amyloid Ξ²-media... | KEEP AS NON CORE | Summary: IGI annotation for positive regulation of tumor necrosis factor production. These immune/inflammatory effects are primarily mediated by Abeta cleavage products activating innate immune cells (microglia, astrocytes) rather than representing core functions of full-length APP. Reason: Immune/inflammatory annotation (positive regulation of tumor necrosis factor production) reflects downstream Abeta-mediated effects. Not a core function of APP itself. Keep as non-core. Supporting Evidence: PMID:22406537 Receptor for advanced glycation end products (RAGE) mediates AΞ²-induced perturbations in cerebral vessels, neurons, and microglia in AD |
| GO:0032760 positive regulation of tumor necrosis factor production | IGI PMID:12808450 RAGE mediates amyloid-beta peptide transport across the bloo... | KEEP AS NON CORE | Summary: IGI annotation for positive regulation of tumor necrosis factor production. These immune/inflammatory effects are primarily mediated by Abeta cleavage products activating innate immune cells (microglia, astrocytes) rather than representing core functions of full-length APP. Reason: Immune/inflammatory annotation (positive regulation of tumor necrosis factor production) reflects downstream Abeta-mediated effects. Not a core function of APP itself. Keep as non-core. Supporting Evidence: PMID:12808450 RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain. |
| GO:1903523 negative regulation of blood circulation | IGI PMID:12808450 RAGE mediates amyloid-beta peptide transport across the bloo... | KEEP AS NON CORE | Summary: IGI annotation for negative regulation of blood circulation. Vascular effects of Abeta peptides including vasoconstriction and endothelin production. These are pathological consequences of Abeta accumulation rather than core APP functions. Reason: Vascular annotation (negative regulation of blood circulation) is a downstream Abeta-mediated pathological effect. Keep as non-core. Supporting Evidence: PMID:12808450 RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain. |
| GO:1904472 positive regulation of endothelin production | IGI PMID:12808450 RAGE mediates amyloid-beta peptide transport across the bloo... | KEEP AS NON CORE | Summary: IGI annotation for positive regulation of endothelin production. Vascular effects of Abeta peptides including vasoconstriction and endothelin production. These are pathological consequences of Abeta accumulation rather than core APP functions. Reason: Vascular annotation (positive regulation of endothelin production) is a downstream Abeta-mediated pathological effect. Keep as non-core. Supporting Evidence: PMID:12808450 RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain. |
| GO:0050786 RAGE receptor binding | IPI P05067-PRO_0000000093 PMID:22406537 A multimodal RAGE-specific inhibitor reduces amyloid Ξ²-media... | ACCEPT | Summary: IPI annotation for Abeta-RAGE binding. Deane et al. (2012) showed a RAGE inhibitor (FPS-ZM1) blocks Abeta binding to the V domain of RAGE, preventing Abeta-induced cellular stress. This is a core molecular interaction of Abeta. Reason: Well-documented Abeta-RAGE interaction. Annotation correctly applies to Abeta cleavage product. RAGE binding is key to Abeta neurotoxicity mechanism. Supporting Evidence: PMID:22406537 we identified a high-affinity RAGE-specific inhibitor (FPS-ZM1) that blocked Abeta binding to the V domain of RAGE |
| GO:1901224 positive regulation of non-canonical NF-kappaB signal transduction | IDA PMID:22406537 A multimodal RAGE-specific inhibitor reduces amyloid Ξ²-media... | KEEP AS NON CORE | Summary: IDA annotation for positive regulation of non-canonical NF-kappaB signal transduction. Abeta-mediated inflammatory signaling. Downstream effect. Reason: NF-kappaB activation is a downstream inflammatory effect of Abeta. Keep as non-core. Supporting Evidence: PMID:22406537 Receptor for advanced glycation end products (RAGE) mediates AΞ²-induced perturbations in cerebral vessels, neurons, and microglia in AD |
| GO:0005798 Golgi-associated vesicle | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on sequence similarity to characterized ortholog. Reason: ISS annotation consistent with known APP functions. |
| GO:0055037 recycling endosome | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on sequence similarity to characterized ortholog. Reason: ISS annotation consistent with known APP functions. |
| GO:0005739 mitochondrion | IDA PMID:23525105 Transcriptional regulation of insulin-degrading enzyme modul... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:23525105 2013 Mar 22. Transcriptional regulation of insulin-degrading enzyme modulates mitochondrial amyloid Ξ² (AΞ²) peptide catabolism and functionality. |
| GO:0005769 early endosome | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on sequence similarity to characterized ortholog. Reason: ISS annotation consistent with known APP functions. |
| GO:0050890 cognition | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation for cognition. Downstream behavioral phenotype of APP/Abeta biology. Not a core molecular function. Reason: Cognition is a high-level phenotype downstream of APP biology. Keep as non-core. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9617595 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0051087 protein-folding chaperone binding | IPI PMID:23106396 Amyloid-Ξ² oligomers are sequestered by both intracellular an... | ACCEPT | Summary: IPI annotation showing specific protein interaction. Reason: IPI annotation with specific molecular function is more informative than generic protein binding. Supporting Evidence: PMID:23106396 Amyloid-Ξ² oligomers are sequestered by both intracellular and extracellular chaperones. |
| GO:0106003 amyloid-beta complex | IPI PMID:22179788 The extracellular chaperone clusterin sequesters oligomeric ... | ACCEPT | Summary: IPI annotation showing specific protein interaction. Reason: IPI annotation with specific molecular function is more informative than generic protein binding. Supporting Evidence: PMID:22179788 The extracellular chaperone clusterin sequesters oligomeric forms of the amyloid-Ξ²(1-40) peptide. |
| GO:0031904 endosome lumen | TAS PMID:24305806 Pharmacologic inhibition of ROCK2 suppresses amyloid-Ξ² produ... | ACCEPT | Summary: TAS annotation based on author statement in referenced publication. Reason: TAS annotation supported by literature. Supporting Evidence: PMID:24305806 Pharmacologic inhibition of ROCK2 suppresses amyloid-Ξ² production in an Alzheimer's disease mouse model. |
| GO:0010628 positive regulation of gene expression | IGI PMID:27853422 ROCK1 Is Associated with Alzheimer's Disease-Specific Plaque... | KEEP AS NON CORE | Summary: IGI annotation for positive regulation of gene expression. Gene expression changes are downstream effects of APP processing and Abeta signaling. Some may be mediated by AICD transcriptional regulation (controversial). Not core APP function. Reason: positive regulation of gene expression is a downstream effect. Keep as non-core. Supporting Evidence: PMID:27853422 eCollection 2016. ROCK1 Is Associated with Alzheimer's Disease-Specific Plaques, as well as Enhances Autophagosome Formation But not Autophagic AΞ² Clearance. |
| GO:0010628 positive regulation of gene expression | IMP PMID:27853422 ROCK1 Is Associated with Alzheimer's Disease-Specific Plaque... | KEEP AS NON CORE | Summary: IMP annotation for positive regulation of gene expression. Gene expression changes are downstream effects of APP processing and Abeta signaling. Some may be mediated by AICD transcriptional regulation (controversial). Not core APP function. Reason: positive regulation of gene expression is a downstream effect. Keep as non-core. Supporting Evidence: PMID:27853422 eCollection 2016. ROCK1 Is Associated with Alzheimer's Disease-Specific Plaques, as well as Enhances Autophagosome Formation But not Autophagic AΞ² Clearance. |
| GO:0010629 negative regulation of gene expression | IGI PMID:27853422 ROCK1 Is Associated with Alzheimer's Disease-Specific Plaque... | KEEP AS NON CORE | Summary: IGI annotation for negative regulation of gene expression. Gene expression changes are downstream effects of APP processing and Abeta signaling. Some may be mediated by AICD transcriptional regulation (controversial). Not core APP function. Reason: negative regulation of gene expression is a downstream effect. Keep as non-core. Supporting Evidence: PMID:27853422 eCollection 2016. ROCK1 Is Associated with Alzheimer's Disease-Specific Plaques, as well as Enhances Autophagosome Formation But not Autophagic AΞ² Clearance. |
| GO:0007611 learning or memory | IMP PMID:15457210 RAGE potentiates Abeta-induced perturbation of neuronal func... | KEEP AS NON CORE | Summary: IMP annotation for learning or memory. APP and its cleavage products (especially Abeta oligomers) affect learning and memory, but this is a downstream phenotypic consequence of APP processing rather than a core molecular function. Reason: learning or memory is a downstream consequence of APP/Abeta biology. Important for disease relevance but not a core function. Keep as non-core. Supporting Evidence: PMID:15457210 Double Tgs (mutant APP (mAPP)/RAGE) displayed early abnormalities in spatial learning/memory, accompanied by altered activation of markers of synaptic plasticity and exaggerated neuropathologic findings, before such changes were found in mAPP mice |
| GO:0007611 learning or memory | IGI PMID:15457210 RAGE potentiates Abeta-induced perturbation of neuronal func... | KEEP AS NON CORE | Summary: IGI annotation for learning or memory. APP and its cleavage products (especially Abeta oligomers) affect learning and memory, but this is a downstream phenotypic consequence of APP processing rather than a core molecular function. Reason: learning or memory is a downstream consequence of APP/Abeta biology. Important for disease relevance but not a core function. Keep as non-core. Supporting Evidence: PMID:15457210 Tg mice bearing a dominant-negative RAGE construct targeted to neurons crossed with mAPP animals displayed preservation of spatial learning/memory |
| GO:0009986 cell surface | NAS PMID:15457210 RAGE potentiates Abeta-induced perturbation of neuronal func... | ACCEPT | Summary: RAGE functions as a cell surface receptor for Abeta. Reason: Paper describes RAGE as signal-transducing cell surface acceptor for Abeta. Supporting Evidence: PMID:15457210 Receptor for Advanced Glycation Endproducts (RAGE), a multiligand receptor in the immunoglobulin superfamily, functions as a signal-transducing cell surface acceptor for amyloid-beta peptide (Abeta) |
| GO:0070374 positive regulation of ERK1 and ERK2 cascade | IGI PMID:15457210 RAGE potentiates Abeta-induced perturbation of neuronal func... | KEEP AS NON CORE | Summary: IGI annotation for positive regulation of ERK1 and ERK2 cascade. Abeta activates MAPK/ERK signaling in various cell types. Downstream signaling effect, not core APP function. Reason: ERK cascade activation is a downstream effect of Abeta. Keep as non-core. Supporting Evidence: PMID:15457210 Receptor for Advanced Glycation Endproducts (RAGE), a multiligand receptor in the immunoglobulin superfamily, functions as a signal-transducing cell surface acceptor for amyloid-beta peptide (Abeta) |
| GO:1990535 neuron projection maintenance | IGI PMID:20445063 Memory impairment in transgenic Alzheimer mice requires cell... | ACCEPT | Summary: IGI annotation based on genetic interaction evidence. NOTE: Many IGI annotations for APP involve Abeta-specific effects from transgenic mouse studies and may not represent full-length APP function. Reason: IGI annotation supported by genetic interaction data. Note potential cleavage product specificity. Supporting Evidence: PMID:20445063 Memory impairment in transgenic Alzheimer mice requires cellular prion protein. |
| GO:0007611 learning or memory | IGI PMID:24052308 Human LilrB2 is a Ξ²-amyloid receptor and its murine homolog ... | KEEP AS NON CORE | Summary: IGI annotation for learning or memory. APP and its cleavage products (especially Abeta oligomers) affect learning and memory, but this is a downstream phenotypic consequence of APP processing rather than a core molecular function. Reason: learning or memory is a downstream consequence of APP/Abeta biology. Important for disease relevance but not a core function. Keep as non-core. Supporting Evidence: PMID:24052308 Human LilrB2 is a Ξ²-amyloid receptor and its murine homolog PirB regulates synaptic plasticity in an Alzheimer's model. |
| GO:0005178 integrin binding | IDA PMID:21126803 Perlecan domain V inhibits Ξ±2 integrin-mediated amyloid-Ξ² ne... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:21126803 Perlecan domain V inhibits Ξ±2 integrin-mediated amyloid-Ξ² neurotoxicity. |
| GO:0005615 extracellular space | IMP PMID:23640054 Brain interstitial oligomeric amyloid Ξ² increases with age a... | ACCEPT | Summary: IMP annotation based on mutant phenotype analysis. Reason: IMP annotation supported by mutant phenotype data. Supporting Evidence: PMID:23640054 Brain interstitial oligomeric amyloid Ξ² increases with age and is resistant to clearance from brain in a mouse model of Alzheimer's disease. |
| GO:0106003 amyloid-beta complex | IMP PMID:23640054 Brain interstitial oligomeric amyloid Ξ² increases with age a... | ACCEPT | Summary: IMP annotation based on mutant phenotype analysis. Reason: IMP annotation supported by mutant phenotype data. Supporting Evidence: PMID:23640054 Brain interstitial oligomeric amyloid Ξ² increases with age and is resistant to clearance from brain in a mouse model of Alzheimer's disease. |
| GO:0050750 low-density lipoprotein particle receptor binding | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on sequence similarity to characterized ortholog. Reason: ISS annotation consistent with known APP functions. |
| GO:0030425 dendrite | IDA NOT PMID:17251419 Abeta oligomer-induced aberrations in synapse composition, s... | ACCEPT | Summary: NOT annotation - Lacor et al. (2007) showed Abeta oligomers (ADDLs) bind to dendritic spines, not dendrite shafts. The annotation indicates where full-length APP or its products are NOT found. This study focused on Abeta oligomer binding specificity to excitatory pyramidal neurons. Reason: The negated annotation accurately captures the spatial specificity of Abeta/ADDL binding shown in PMID:17251419. Supporting Evidence: PMID:17251419 ADDLs bound to neurons with specificity, attaching to presumed excitatory pyramidal neurons but not GABAergic neurons... consistent with observed attachment of ADDLs to dendritic spines. |
| GO:0032590 dendrite membrane | TAS NOT PMID:20032460 Inhibition of calcineurin-mediated endocytosis and alpha-ami... | ACCEPT | Summary: NOT annotation - Zhao et al. (2010) showed that Abeta oligomers (ADDLs) bind specifically to dendritic spines expressing surface AMPA receptors (particularly GluR2), not the general dendrite membrane. The specificity is for postsynaptic compartments. Reason: The negated annotation accurately reflects the spatial selectivity of ADDL binding shown in PMID:20032460. Supporting Evidence: PMID:20032460 ADDL binding occurs in dendritic spines that express surface AMPA receptors, particularly the calcium-impermeable type II AMPA receptor subunit (GluR2). |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9010034 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9010034 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9010091 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0031904 endosome lumen | TAS Reactome:R-HSA-5692495 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0031904 endosome lumen | TAS Reactome:R-HSA-9010096 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0005615 extracellular space | IDA PMID:23921129 FcΞ³RIIb mediates amyloid-Ξ² neurotoxicity and memory impairme... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:23921129 soluble AΞ² oligomers interact with FcΞ³RIIb in vitro and in AD brains |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IGI PMID:23921129 FcΞ³RIIb mediates amyloid-Ξ² neurotoxicity and memory impairme... | KEEP AS NON CORE | Summary: IGI annotation for positive regulation of transcription by RNA polymerase II. AICD has been reported to regulate transcription through Fe65/Tip60 complex, but this remains controversial and applies to a cleavage product rather than full-length APP. Reason: Transcriptional regulation by AICD is controversial and represents a cleavage product function. Keep as non-core. Supporting Evidence: PMID:23921129 FcΞ³RIIb is significantly upregulated in the hippocampus of AD brains and neuronal cells exposed to synthetic AΞ² |
| GO:0007611 learning or memory | IGI PMID:21113149 Reversing EphB2 depletion rescues cognitive functions in Alz... | KEEP AS NON CORE | Summary: IGI annotation for learning or memory. APP and its cleavage products (especially Abeta oligomers) affect learning and memory, but this is a downstream phenotypic consequence of APP processing rather than a core molecular function. Reason: learning or memory is a downstream consequence of APP/Abeta biology. Important for disease relevance but not a core function. Keep as non-core. Supporting Evidence: PMID:21113149 Reversing EphB2 depletion rescues cognitive functions in Alzheimer model. |
| GO:0097645 amylin binding | TAS PMID:22500019 Amyloid Ξ² (AΞ²) peptide directly activates amylin-3 receptor ... | ACCEPT | Summary: TAS annotation based on author statement in referenced publication. Reason: TAS annotation supported by literature. Supporting Evidence: PMID:22500019 2012 Apr 12. Amyloid Ξ² (AΞ²) peptide directly activates amylin-3 receptor subtype by triggering multiple intracellular signaling pathways. |
| GO:0010628 positive regulation of gene expression | IGI PMID:22198949 TLR2 is a primary receptor for Alzheimer's amyloid Ξ² peptide... | KEEP AS NON CORE | Summary: IGI annotation for positive regulation of gene expression. Gene expression changes are downstream effects of APP processing and Abeta signaling. Some may be mediated by AICD transcriptional regulation (controversial). Not core APP function. Reason: positive regulation of gene expression is a downstream effect. Keep as non-core. Supporting Evidence: PMID:22198949 TLR2-mediated AΞ²42-triggered inflammatory activation |
| GO:0010629 negative regulation of gene expression | IGI PMID:22198949 TLR2 is a primary receptor for Alzheimer's amyloid Ξ² peptide... | KEEP AS NON CORE | Summary: IGI annotation for negative regulation of gene expression. Gene expression changes are downstream effects of APP processing and Abeta signaling. Some may be mediated by AICD transcriptional regulation (controversial). Not core APP function. Reason: negative regulation of gene expression is a downstream effect. Keep as non-core. Supporting Evidence: PMID:22198949 TLR2 deficiency in microglia shifts M1- to M2-inflammatory activation in vivo |
| GO:0005769 early endosome | IDA PMID:26005850 Central role for PICALM in amyloid-Ξ² blood-brain barrier tra... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:26005850 guided AΞ² trafficking to Rab5 and Rab11 |
| GO:0070381 endosome to plasma membrane transport vesicle | IDA PMID:26005850 Central role for PICALM in amyloid-Ξ² blood-brain barrier tra... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:26005850 leading to AΞ² endothelial transcytosis and clearance |
| GO:0005615 extracellular space | IDA PMID:26005850 Central role for PICALM in amyloid-Ξ² blood-brain barrier tra... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:26005850 AΞ² clearance across the murine blood-brain barrier (BBB) |
| GO:0048143 astrocyte activation | IGI PMID:20445063 Memory impairment in transgenic Alzheimer mice requires cell... | KEEP AS NON CORE | Summary: IGI annotation for astrocyte activation. These immune/inflammatory effects are primarily mediated by Abeta cleavage products activating innate immune cells (microglia, astrocytes) rather than representing core functions of full-length APP. Reason: Immune/inflammatory annotation (astrocyte activation) reflects downstream Abeta-mediated effects. Not a core function of APP itself. Keep as non-core. Supporting Evidence: PMID:20445063 Memory impairment in transgenic Alzheimer mice requires cellular prion protein. |
| GO:0005109 frizzled binding | IPI PMID:18234671 Amyloid-beta binds to the extracellular cysteine-rich domain... | ACCEPT | Summary: Abeta binds to the Frizzled cysteine-rich domain at or near the Wnt-binding site. Reason: IPI annotation with specific molecular function is more informative than generic protein binding. Supporting Evidence: PMID:18234671 Abeta binds to the Fz cysteine-rich domain at or in close proximity to the Wnt-binding site and inhibits the canonical Wnt signaling pathway |
| GO:0010629 negative regulation of gene expression | IGI PMID:18234671 Amyloid-beta binds to the extracellular cysteine-rich domain... | KEEP AS NON CORE | Summary: IGI annotation for negative regulation of gene expression. Gene expression changes are downstream effects of APP processing and Abeta signaling. Some may be mediated by AICD transcriptional regulation (controversial). Not core APP function. Reason: negative regulation of gene expression is a downstream effect. Keep as non-core. Supporting Evidence: PMID:18234671 Amyloid-beta binds to the extracellular cysteine-rich domain of Frizzled and inhibits Wnt/beta-catenin signaling |
| GO:0090090 negative regulation of canonical Wnt signaling pathway | IDA PMID:18234671 Amyloid-beta binds to the extracellular cysteine-rich domain... | KEEP AS NON CORE | Summary: IDA annotation for negative regulation of canonical Wnt signaling pathway. APP/Abeta interaction with Wnt signaling components. Not core function. Reason: Wnt signaling regulation is not a core function of APP. Keep as non-core. Supporting Evidence: PMID:18234671 Abeta binds to the Fz cysteine-rich domain at or in close proximity to the Wnt-binding site and inhibits the canonical Wnt signaling pathway |
| GO:1900181 negative regulation of protein localization to nucleus | IGI PMID:18234671 Amyloid-beta binds to the extracellular cysteine-rich domain... | ACCEPT | Summary: By inhibiting Wnt signaling, Abeta prevents beta-catenin nuclear localization required for Wnt target gene activation. Reason: IGI annotation reflects Abeta blocking beta-catenin nuclear translocation by inhibiting Wnt signaling. Supporting Evidence: PMID:18234671 Amyloid-beta binds to the extracellular cysteine-rich domain of Frizzled and inhibits Wnt/beta-catenin signaling |
| GO:0002265 astrocyte activation involved in immune response | IGI PMID:23152628 LRP1 in brain vascular smooth muscle cells mediates local cl... | KEEP AS NON CORE | Summary: IGI annotation for astrocyte activation involved in immune response. These immune/inflammatory effects are primarily mediated by Abeta cleavage products activating innate immune cells (microglia, astrocytes) rather than representing core functions of full-length APP. Reason: Immune/inflammatory annotation (astrocyte activation involved in immune response) reflects downstream Abeta-mediated effects. Not a core function of APP itself. Keep as non-core. Supporting Evidence: PMID:23152628 LRP1 in brain vascular smooth muscle cells mediates local clearance of Alzheimer's amyloid-Ξ². |
| GO:0005764 lysosome | IDA PMID:23152628 LRP1 in brain vascular smooth muscle cells mediates local cl... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:23152628 LRP1 in brain vascular smooth muscle cells mediates local clearance of Alzheimer's amyloid-Ξ². |
| GO:0043395 heparan sulfate proteoglycan binding | IMP PMID:21289173 Heparan sulphate proteoglycan and the low-density lipoprotei... | ACCEPT | Summary: IMP annotation based on mutant phenotype analysis. Reason: IMP annotation supported by mutant phenotype data. Supporting Evidence: PMID:21289173 Heparan sulphate proteoglycan and the low-density lipoprotein receptor-related protein 1 constitute major pathways for neuronal amyloid-beta uptake. |
| GO:1904399 heparan sulfate binding | TAS PMID:21289173 Heparan sulphate proteoglycan and the low-density lipoprotei... | ACCEPT | Summary: TAS annotation based on author statement in referenced publication. Reason: TAS annotation supported by literature. Supporting Evidence: PMID:21289173 Heparan sulphate proteoglycan and the low-density lipoprotein receptor-related protein 1 constitute major pathways for neuronal amyloid-beta uptake. |
| GO:1904646 cellular response to amyloid-beta | IGI PMID:23152628 LRP1 in brain vascular smooth muscle cells mediates local cl... | ACCEPT | Summary: IGI annotation based on genetic interaction evidence. NOTE: Many IGI annotations for APP involve Abeta-specific effects from transgenic mouse studies and may not represent full-length APP function. Reason: IGI annotation supported by genetic interaction data. Note potential cleavage product specificity. Supporting Evidence: PMID:23152628 LRP1 in brain vascular smooth muscle cells mediates local clearance of Alzheimer's amyloid-Ξ². |
| GO:0032991 protein-containing complex | IDA PMID:9228033 Interaction of apolipoprotein J-amyloid beta-peptide complex... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:9228033 Interaction of apolipoprotein J-amyloid beta-peptide complex with low density lipoprotein receptor-related protein-2/megalin. |
| GO:0034185 apolipoprotein binding | IPI PMID:22138302 Preferential interactions between ApoE-containing lipoprotei... | ACCEPT | Summary: IPI annotation showing specific protein interaction. Reason: IPI annotation with specific molecular function is more informative than generic protein binding. Supporting Evidence: PMID:22138302 Preferential interactions between ApoE-containing lipoproteins and AΞ² revealed by a detection method that combines size exclusion chromatography with non-reducing gel-shift. |
| GO:0034363 intermediate-density lipoprotein particle | IDA PMID:22138302 Preferential interactions between ApoE-containing lipoprotei... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:22138302 Preferential interactions between ApoE-containing lipoproteins and AΞ² revealed by a detection method that combines size exclusion chromatography with non-reducing gel-shift. |
| GO:0034364 high-density lipoprotein particle | IDA PMID:22138302 Preferential interactions between ApoE-containing lipoprotei... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:22138302 Preferential interactions between ApoE-containing lipoproteins and AΞ² revealed by a detection method that combines size exclusion chromatography with non-reducing gel-shift. |
| GO:0051087 protein-folding chaperone binding | IPI PMID:9228033 Interaction of apolipoprotein J-amyloid beta-peptide complex... | ACCEPT | Summary: IPI annotation showing specific protein interaction. Reason: IPI annotation with specific molecular function is more informative than generic protein binding. Supporting Evidence: PMID:9228033 Interaction of apolipoprotein J-amyloid beta-peptide complex with low density lipoprotein receptor-related protein-2/megalin. |
| GO:1990777 lipoprotein particle | IDA PMID:22138302 Preferential interactions between ApoE-containing lipoprotei... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:22138302 Preferential interactions between ApoE-containing lipoproteins and AΞ² revealed by a detection method that combines size exclusion chromatography with non-reducing gel-shift. |
| GO:0010628 positive regulation of gene expression | IMP PMID:23164821 Clusterin regulates Ξ²-amyloid toxicity via Dickkopf-1-driven... | KEEP AS NON CORE | Summary: IMP annotation for positive regulation of gene expression. Gene expression changes are downstream effects of APP processing and Abeta signaling. Some may be mediated by AICD transcriptional regulation (controversial). Not core APP function. Reason: positive regulation of gene expression is a downstream effect. Keep as non-core. Supporting Evidence: PMID:23164821 AΞ² induction of DKK1 and all five of the common genes, including EGR1, NAB2 and KLF10, was significantly blocked by the silencing of CLU |
| GO:0008285 negative regulation of cell population proliferation | IDA PMID:22944668 Antimicrobial activity of human islet amyloid polypeptides: ... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:22944668 Antimicrobial activity of human islet amyloid polypeptides: an insight into amyloid peptides' connection with antimicrobial peptides. |
| GO:0034185 apolipoprotein binding | IPI PMID:9211985 Association of human, rat, and rabbit apolipoprotein E with ... | ACCEPT | Summary: IPI annotation showing specific protein interaction. Reason: IPI annotation with specific molecular function is more informative than generic protein binding. Supporting Evidence: PMID:9211985 These binding studies provide one possible explanation for protective effects of both apoE2 and E3 against the development of Alzheimer's disease |
| GO:0042157 lipoprotein metabolic process | IC PMID:9211985 Association of human, rat, and rabbit apolipoprotein E with ... | ACCEPT | Summary: IC annotation inferred by curator based on available evidence. Reason: IC annotation supported by curator judgment. Supporting Evidence: PMID:9211985 In humans, apolipoprotein E (apoE) has three major isoforms |
| GO:0098815 modulation of excitatory postsynaptic potential | IGI PMID:20974225 Activation of nicotinic Ξ±(7) acetylcholine receptor enhances... | ACCEPT | Summary: IGI annotation based on genetic interaction evidence. NOTE: Many IGI annotations for APP involve Abeta-specific effects from transgenic mouse studies and may not represent full-length APP function. Reason: IGI annotation supported by genetic interaction data. Note potential cleavage product specificity. Supporting Evidence: PMID:20974225 Epub 2010 Oct 23. Activation of nicotinic Ξ±(7) acetylcholine receptor enhances long term potentation in wild type mice but not in APP(swe)/PS1ΞE9 mice. |
| GO:1900273 positive regulation of long-term synaptic potentiation | IGI PMID:20974225 Activation of nicotinic Ξ±(7) acetylcholine receptor enhances... | ACCEPT | Summary: IGI annotation based on genetic interaction evidence. NOTE: Many IGI annotations for APP involve Abeta-specific effects from transgenic mouse studies and may not represent full-length APP function. Reason: IGI annotation supported by genetic interaction data. Note potential cleavage product specificity. Supporting Evidence: PMID:20974225 Epub 2010 Oct 23. Activation of nicotinic Ξ±(7) acetylcholine receptor enhances long term potentation in wild type mice but not in APP(swe)/PS1ΞE9 mice. |
| GO:0097060 synaptic membrane | IDA NOT PMID:17308309 Abeta oligomers induce neuronal oxidative stress through an ... | ACCEPT | Summary: NOT annotation - De Felice et al. (2007) showed Abeta oligomers (ADDLs) bind specifically at or near NMDA receptors, not the general synaptic membrane. The study showed ADDLs co-immunoprecipitate with NMDA-R subunits and require NMDA-R activation for their effects. Reason: The negated annotation accurately captures the receptor-specific binding of ADDLs shown in PMID:17308309, distinguishing binding specificity from general synaptic membrane localization. Supporting Evidence: PMID:17308309 ADDLs that were bound to detergent-extracted synaptosomal membranes co-immunoprecipitated with NMDA-R subunits... ADDLs bind to or in close proximity to NMDA-Rs, triggering neuronal damage through NMDA-R-dependent calcium flux. |
| GO:0032991 protein-containing complex | IPI P05067-PRO_0000000093 PMID:18568035 Amyloid-beta protein dimers isolated directly from Alzheimer... | ACCEPT | Summary: IPI annotation for Abeta complex formation. Shankar et al. (2008) showed that Abeta dimers (Abeta42-Abeta40 complexes) are the minimal synaptotoxic species. The IPI annotation correctly captures that Abeta42 forms complexes with Abeta40. Reason: Well-supported IPI annotation correctly targeting Abeta cleavage product. Dimerization is essential for synaptotoxicity. Supporting Evidence: PMID:18568035 These various effects were specifically attributable to Abeta dimers |
| GO:0061844 antimicrobial humoral immune response mediated by antimicrobial peptide | IMP PMID:20209079 The Alzheimer's disease-associated amyloid beta-protein is a... | KEEP AS NON CORE | Summary: IMP annotation for antimicrobial humoral immune response mediated by antimicrobial peptide. These immune/inflammatory effects are primarily mediated by Abeta cleavage products activating innate immune cells (microglia, astrocytes) rather than representing core functions of full-length APP. Reason: Immune/inflammatory annotation (antimicrobial humoral immune response mediated by antimicrobial peptide) reflects downstream Abeta-mediated effects. Not a core function of APP itself. Keep as non-core. Supporting Evidence: PMID:20209079 Abeta exerts antimicrobial activity against eight common and clinically relevant microorganisms with a potency equivalent to, and in some cases greater than, LL-37 |
| GO:0046982 protein heterodimerization activity | IPI P05067-PRO_0000000093 PMID:18568035 Amyloid-beta protein dimers isolated directly from Alzheimer... | ACCEPT | Summary: IPI annotation for Abeta heterodimerization. GOA shows Abeta42 (PRO_0000000093) heterodimerizes with Abeta40 (PRO_0000000092). Shankar et al. (2008) demonstrated that Abeta dimers are the smallest synaptotoxic species. Reason: Well-supported IPI annotation correctly targeting Abeta42. The Abeta42-Abeta40 heterodimer is the pathogenic species. Supporting Evidence: PMID:18568035 These various effects were specifically attributable to Abeta dimers |
| GO:0051247 positive regulation of protein metabolic process | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS annotation based on sequence similarity to characterized ortholog, but the term is very broad and does not identify the specific APP-dependent processing, trafficking, or fragment-mediated mechanism. Reason: GO:0051247 is too broad for informative APP curation and should not be promoted as a core function when more specific APP biology is available. |
| GO:0005886 plasma membrane | IDA PMID:20164328 Loss of alpha7 nicotinic receptors enhances beta-amyloid oli... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:20164328 Loss of alpha7 nicotinic receptors enhances beta-amyloid oligomer accumulation, exacerbating early-stage cognitive decline and septohippocampal pathology in a mouse model of Alzheimer's disease. |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-8952289 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0007611 learning or memory | IGI PMID:19587288 Deletion of the alpha 7 nicotinic acetylcholine receptor gen... | KEEP AS NON CORE | Summary: IGI annotation for learning or memory. APP and its cleavage products (especially Abeta oligomers) affect learning and memory, but this is a downstream phenotypic consequence of APP processing rather than a core molecular function. Reason: learning or memory is a downstream consequence of APP/Abeta biology. Important for disease relevance but not a core function. Keep as non-core. Supporting Evidence: PMID:19587288 Deletion of the alpha 7 nicotinic acetylcholine receptor gene improves cognitive deficits and synaptic pathology in a mouse model of Alzheimer's disease. |
| GO:0050808 synapse organization | IGI PMID:19587288 Deletion of the alpha 7 nicotinic acetylcholine receptor gen... | ACCEPT | Summary: IGI annotation based on genetic interaction evidence. NOTE: Many IGI annotations for APP involve Abeta-specific effects from transgenic mouse studies and may not represent full-length APP function. Reason: IGI annotation supported by genetic interaction data. Note potential cleavage product specificity. Supporting Evidence: PMID:19587288 Deletion of the alpha 7 nicotinic acetylcholine receptor gene improves cognitive deficits and synaptic pathology in a mouse model of Alzheimer's disease. |
| GO:0005796 Golgi lumen | TAS Reactome:R-HSA-8871506 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:1990000 amyloid fibril formation | IMP PMID:25620700 A genome-wide gene-expression analysis and database in trans... | ACCEPT | Summary: IMP annotation based on mutant phenotype analysis. Reason: IMP annotation supported by mutant phenotype data. Supporting Evidence: PMID:25620700 2015 Jan 22. A genome-wide gene-expression analysis and database in transgenic mice during development of amyloid or tau pathology. |
| GO:0001878 response to yeast | IMP PMID:20209079 The Alzheimer's disease-associated amyloid beta-protein is a... | KEEP AS NON CORE | Summary: IMP annotation for response to yeast. These immune/inflammatory effects are primarily mediated by Abeta cleavage products activating innate immune cells (microglia, astrocytes) rather than representing core functions of full-length APP. Reason: Immune/inflammatory annotation (response to yeast) reflects downstream Abeta-mediated effects. Not a core function of APP itself. Keep as non-core. Supporting Evidence: PMID:20209079 anti-Abeta immunoreactive material in AD whole brain homogenates is active against Candida albicans, the pathogen we identified as most sensitive to synthetic Abeta |
| GO:0019731 antibacterial humoral response | IDA PMID:20209079 The Alzheimer's disease-associated amyloid beta-protein is a... | KEEP AS NON CORE | Summary: IDA annotation for antibacterial humoral response. These immune/inflammatory effects are primarily mediated by Abeta cleavage products activating innate immune cells (microglia, astrocytes) rather than representing core functions of full-length APP. Reason: Immune/inflammatory annotation (antibacterial humoral response) reflects downstream Abeta-mediated effects. Not a core function of APP itself. Keep as non-core. Supporting Evidence: PMID:20209079 Abeta exerts antimicrobial activity against eight common and clinically relevant microorganisms with a potency equivalent to, and in some cases greater than, LL-37 |
| GO:0019732 antifungal humoral response | IMP PMID:20209079 The Alzheimer's disease-associated amyloid beta-protein is a... | KEEP AS NON CORE | Summary: IMP annotation for antifungal humoral response. These immune/inflammatory effects are primarily mediated by Abeta cleavage products activating innate immune cells (microglia, astrocytes) rather than representing core functions of full-length APP. Reason: Immune/inflammatory annotation (antifungal humoral response) reflects downstream Abeta-mediated effects. Not a core function of APP itself. Keep as non-core. Supporting Evidence: PMID:20209079 anti-Abeta immunoreactive material in AD whole brain homogenates is active against Candida albicans, the pathogen we identified as most sensitive to synthetic Abeta |
| GO:0045087 innate immune response | IMP PMID:20209079 The Alzheimer's disease-associated amyloid beta-protein is a... | KEEP AS NON CORE | Summary: IMP annotation for innate immune response. These immune/inflammatory effects are primarily mediated by Abeta cleavage products activating innate immune cells (microglia, astrocytes) rather than representing core functions of full-length APP. Reason: Immune/inflammatory annotation (innate immune response) reflects downstream Abeta-mediated effects. Not a core function of APP itself. Keep as non-core. Supporting Evidence: PMID:20209079 Our findings suggest Abeta is a hitherto unrecognized AMP that may normally function in the innate immune system |
| GO:0050829 defense response to Gram-negative bacterium | IDA PMID:20209079 The Alzheimer's disease-associated amyloid beta-protein is a... | KEEP AS NON CORE | Summary: IDA annotation for defense response to Gram-negative bacterium. These immune/inflammatory effects are primarily mediated by Abeta cleavage products activating innate immune cells (microglia, astrocytes) rather than representing core functions of full-length APP. Reason: Immune/inflammatory annotation (defense response to Gram-negative bacterium) reflects downstream Abeta-mediated effects. Not a core function of APP itself. Keep as non-core. Supporting Evidence: PMID:20209079 The synthetic Abeta peptides demonstrated antibiotic activity against Gram-negative and Gram-positive bacteria and the yeast C. albicans |
| GO:0050830 defense response to Gram-positive bacterium | IDA PMID:20209079 The Alzheimer's disease-associated amyloid beta-protein is a... | KEEP AS NON CORE | Summary: IDA annotation for defense response to Gram-positive bacterium. These immune/inflammatory effects are primarily mediated by Abeta cleavage products activating innate immune cells (microglia, astrocytes) rather than representing core functions of full-length APP. Reason: Immune/inflammatory annotation (defense response to Gram-positive bacterium) reflects downstream Abeta-mediated effects. Not a core function of APP itself. Keep as non-core. Supporting Evidence: PMID:20209079 The synthetic Abeta peptides demonstrated antibiotic activity against Gram-negative and Gram-positive bacteria and the yeast C. albicans |
| GO:0031904 endosome lumen | TAS Reactome:R-HSA-6783332 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0005515 protein binding | IPI PMID:11238726 Fibulin-1 binds the amino-terminal head of beta-amyloid prec... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:11238726 Fibulin-1 binds the amino-terminal head of beta-amyloid precursor protein and modulates its physiological function. |
| GO:0005768 endosome | IDA PMID:18353773 A novel sorting nexin modulates endocytic trafficking and al... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:18353773 2008 Mar 19. A novel sorting nexin modulates endocytic trafficking and alpha-secretase cleavage of the amyloid precursor protein. |
| GO:0009986 cell surface | IDA PMID:18353773 A novel sorting nexin modulates endocytic trafficking and al... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:18353773 2008 Mar 19. A novel sorting nexin modulates endocytic trafficking and alpha-secretase cleavage of the amyloid precursor protein. |
| GO:0005515 protein binding | IPI PMID:24336208 Rare coding variants in the phospholipase D3 gene confer ris... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:24336208 Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer's disease. |
| GO:0005615 extracellular space | HDA PMID:16502470 Human colostrum: identification of minor proteins in the aqu... | ACCEPT | Summary: HDA annotation from high-throughput direct assay. Reason: HDA annotation supported by experimental data. Supporting Evidence: PMID:16502470 Human colostrum: identification of minor proteins in the aqueous phase by proteomics. |
| GO:0019899 enzyme binding | IPI PMID:24499793 FKBP12 regulates the localization and processing of amyloid ... | ACCEPT | Summary: IPI annotation showing specific protein interaction. Reason: IPI annotation with specific molecular function is more informative than generic protein binding. Supporting Evidence: PMID:24499793 FKBP12 regulates the localization and processing of amyloid precursor protein in human cell lines. |
| GO:0045121 membrane raft | IDA PMID:24499793 FKBP12 regulates the localization and processing of amyloid ... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:24499793 FKBP12 regulates the localization and processing of amyloid precursor protein in human cell lines. |
| GO:0005515 protein binding | IPI PMID:16407538 Interaction of the cytosolic domains of sorLA/LR11 with the ... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:16407538 Interaction of the cytosolic domains of sorLA/LR11 with the amyloid precursor protein (APP) and beta-secretase beta-site APP-cleaving enzyme. |
| GO:0005641 nuclear envelope lumen | IDA PMID:21989385 Quantitative modelling of amyloidogenic processing and its i... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:21989385 Quantitative modelling of amyloidogenic processing and its influence by SORLA in Alzheimer's disease. |
| GO:0043235 receptor complex | IDA PMID:23382219 Structural basis for endosomal trafficking of diverse transm... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:23382219 Structural basis for endosomal trafficking of diverse transmembrane cargos by PX-FERM proteins. |
| GO:0070062 extracellular exosome | HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid... | ACCEPT | Summary: HDA annotation from high-throughput direct assay. Reason: HDA annotation supported by experimental data. Supporting Evidence: PMID:19199708 Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT). |
| GO:0005794 Golgi apparatus | IDA PMID:20427278 The novel membrane protein TMEM59 modulates complex glycosyl... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:20427278 2010 Apr 28. The novel membrane protein TMEM59 modulates complex glycosylation, cell surface expression, and secretion of the amyloid precursor protein. |
| GO:0005886 plasma membrane | IDA PMID:20427278 The novel membrane protein TMEM59 modulates complex glycosyl... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:20427278 2010 Apr 28. The novel membrane protein TMEM59 modulates complex glycosylation, cell surface expression, and secretion of the amyloid precursor protein. |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:20427278 The novel membrane protein TMEM59 modulates complex glycosyl... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:20427278 2010 Apr 28. The novel membrane protein TMEM59 modulates complex glycosylation, cell surface expression, and secretion of the amyloid precursor protein. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-481007 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1296421 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-844440 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-844610 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-844612 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0031093 platelet alpha granule lumen | TAS Reactome:R-HSA-481007 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0031904 endosome lumen | TAS Reactome:R-HSA-5229111 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0031904 endosome lumen | TAS Reactome:R-HSA-8871494 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0031904 endosome lumen | TAS Reactome:R-HSA-8871506 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0031904 endosome lumen | TAS Reactome:R-HSA-9010091 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0032588 trans-Golgi network membrane | TAS Reactome:R-HSA-5229111 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0032588 trans-Golgi network membrane | TAS Reactome:R-HSA-5229132 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2467665 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6783332 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-879411 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-976734 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-977136 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0005576 extracellular region | TAS Reactome:R-NUL-997411 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-379048 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-380073 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-391913 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-749448 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-749452 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-749454 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-749456 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8870710 | ACCEPT | Summary: TAS annotation from Reactome pathway database. Reason: Reactome annotation consistent with known APP biology and pathway involvement. |
| GO:0005515 protein binding | IPI PMID:18468999 Regulation of FE65 nuclear translocation and function by amy... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:18468999 2008 May 9. Regulation of FE65 nuclear translocation and function by amyloid beta-protein precursor in osmotically stressed cells. |
| GO:0005886 plasma membrane | IDA PMID:12805363 Autosomal recessive hypercholesterolemia protein interacts w... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:12805363 2003 Jun 12. Autosomal recessive hypercholesterolemia protein interacts with and regulates the cell surface level of Alzheimer's amyloid beta precursor protein. |
| GO:0051425 PTB domain binding | IPI PMID:12805363 Autosomal recessive hypercholesterolemia protein interacts w... | ACCEPT | Summary: IPI annotation showing specific protein interaction. Reason: IPI annotation with specific molecular function is more informative than generic protein binding. Supporting Evidence: PMID:12805363 2003 Jun 12. Autosomal recessive hypercholesterolemia protein interacts with and regulates the cell surface level of Alzheimer's amyloid beta precursor protein. |
| GO:0005515 protein binding | IPI PMID:18509662 Close association of water channel AQP1 with amyloid-beta de... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:18509662 2008 May 29. Close association of water channel AQP1 with amyloid-beta deposition in Alzheimer disease brains. |
| GO:0005737 cytoplasm | IDA PMID:18509662 Close association of water channel AQP1 with amyloid-beta de... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:18509662 2008 May 29. Close association of water channel AQP1 with amyloid-beta deposition in Alzheimer disease brains. |
| GO:0005102 signaling receptor binding | IPI PMID:19849849 CD74 interacts with APP and suppresses the production of Abe... | ACCEPT | Summary: IPI annotation showing specific protein interaction. Reason: IPI annotation with specific molecular function is more informative than generic protein binding. Supporting Evidence: PMID:19849849 CD74 interacts with APP and suppresses the production of Abeta. |
| GO:0005515 protein binding | IPI PMID:19849849 CD74 interacts with APP and suppresses the production of Abe... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:19849849 CD74 interacts with APP and suppresses the production of Abeta. |
| GO:0005515 protein binding | IPI PMID:19901339 RAGE-mediated signaling contributes to intraneuronal transpo... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:19901339 RAGE-mediated signaling contributes to intraneuronal transport of amyloid-beta and neuronal dysfunction. |
| GO:0043197 dendritic spine | IDA PMID:11988176 The acid-activated ion channel ASIC contributes to synaptic ... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:11988176 The acid-activated ion channel ASIC contributes to synaptic plasticity, learning, and memory. |
| GO:0043198 dendritic shaft | IDA PMID:11988176 The acid-activated ion channel ASIC contributes to synaptic ... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:11988176 The acid-activated ion channel ASIC contributes to synaptic plasticity, learning, and memory. |
| GO:0045202 synapse | IDA PMID:11988176 The acid-activated ion channel ASIC contributes to synaptic ... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:11988176 The acid-activated ion channel ASIC contributes to synaptic plasticity, learning, and memory. |
| GO:0003677 DNA binding | ISS GO_REF:0000024 | UNDECIDED | Summary: ISS annotation for DNA binding. The AICD fragment has been reported to associate with transcription factor complexes (Fe65/Tip60) and regulate gene expression, but whether AICD itself directly binds DNA remains controversial. Most evidence suggests AICD acts as a transcriptional co-activator through protein-protein interactions rather than direct DNA binding. Reason: The claim that APP/AICD directly binds DNA is not well-supported. AICD associates with DNA-binding complexes but may not bind DNA directly. This annotation needs further experimental validation. |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on sequence similarity to characterized ortholog. Reason: ISS annotation consistent with known APP functions. |
| GO:0005794 Golgi apparatus | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on sequence similarity to characterized ortholog. Reason: ISS annotation consistent with known APP functions. |
| GO:0006417 regulation of translation | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on sequence similarity to characterized ortholog. Reason: ISS annotation consistent with known APP functions. |
| GO:0006878 intracellular copper ion homeostasis | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on sequence similarity to characterized ortholog. Reason: ISS annotation consistent with known APP functions. |
| GO:0006897 endocytosis | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on sequence similarity to characterized ortholog. Reason: ISS annotation consistent with known APP functions. |
| GO:0007409 axonogenesis | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on sequence similarity to characterized ortholog. Reason: ISS annotation consistent with known APP functions. |
| GO:0007617 mating behavior | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation for mating behavior based on mouse APP knockout/transgenic studies. These behavioral phenotypes reflect pleiotropic downstream effects of APP loss or Abeta overexpression in mice rather than a core molecular function of APP. Reason: Behavioral phenotype (mating behavior) observed in mouse models. Not a core function of APP but a downstream consequence. Keep as non-core. |
| GO:0007626 locomotory behavior | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation for locomotory behavior based on mouse APP knockout/transgenic studies. These behavioral phenotypes reflect pleiotropic downstream effects of APP loss or Abeta overexpression in mice rather than a core molecular function of APP. Reason: Behavioral phenotype (locomotory behavior) observed in mouse models. Not a core function of APP but a downstream consequence. Keep as non-core. |
| GO:0008088 axo-dendritic transport | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on sequence similarity to characterized ortholog. Reason: ISS annotation consistent with known APP functions. |
| GO:0008344 adult locomotory behavior | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation for adult locomotory behavior based on mouse APP knockout/transgenic studies. These behavioral phenotypes reflect pleiotropic downstream effects of APP loss or Abeta overexpression in mice rather than a core molecular function of APP. Reason: Behavioral phenotype (adult locomotory behavior) observed in mouse models. Not a core function of APP but a downstream consequence. Keep as non-core. |
| GO:0008542 visual learning | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation for visual learning based on mouse APP knockout/transgenic studies. These behavioral phenotypes reflect pleiotropic downstream effects of APP loss or Abeta overexpression in mice rather than a core molecular function of APP. Reason: Behavioral phenotype (visual learning) observed in mouse models. Not a core function of APP but a downstream consequence. Keep as non-core. |
| GO:0016020 membrane | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on sequence similarity to characterized ortholog. Reason: ISS annotation consistent with known APP functions. |
| GO:0016199 axon midline choice point recognition | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on sequence similarity to characterized ortholog. Reason: ISS annotation consistent with known APP functions. |
| GO:0016322 neuron remodeling | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on sequence similarity to characterized ortholog. Reason: ISS annotation consistent with known APP functions. |
| GO:0016358 dendrite development | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on sequence similarity to characterized ortholog. Reason: ISS annotation consistent with known APP functions. |
| GO:0030198 extracellular matrix organization | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on sequence similarity to characterized ortholog. Reason: ISS annotation consistent with known APP functions. |
| GO:0030424 axon | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on sequence similarity to characterized ortholog. Reason: ISS annotation consistent with known APP functions. |
| GO:0031175 neuron projection development | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on sequence similarity to characterized ortholog. Reason: ISS annotation consistent with known APP functions. |
| GO:0035235 ionotropic glutamate receptor signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on sequence similarity to characterized ortholog. Reason: ISS annotation consistent with known APP functions. |
| GO:0040014 regulation of multicellular organism growth | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on sequence similarity to characterized ortholog. Reason: ISS annotation consistent with known APP functions. |
| GO:0045931 positive regulation of mitotic cell cycle | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation for positive regulation of mitotic cell cycle. Some evidence suggests AICD can regulate cell cycle genes, but this is not a core function of APP in neurons (which are post-mitotic). Reason: Cell cycle regulation is not a core function of APP, particularly in neurons which are post-mitotic. Keep as non-core. |
| GO:0048669 collateral sprouting in absence of injury | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on sequence similarity to characterized ortholog. Reason: ISS annotation consistent with known APP functions. |
| GO:0050803 regulation of synapse structure or activity | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on sequence similarity to characterized ortholog. Reason: ISS annotation consistent with known APP functions. |
| GO:0005515 protein binding | IPI PMID:18026102 Cystatin C modulates cerebral beta-amyloidosis. | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:18026102 Cystatin C modulates cerebral beta-amyloidosis. |
| GO:0005515 protein binding | IPI PMID:14557245 APP-BP1 mediates APP-induced apoptosis and DNA synthesis and... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:14557245 APP-BP1 mediates APP-induced apoptosis and DNA synthesis and is increased in Alzheimer's disease brain. |
| GO:0005515 protein binding | IPI PMID:8626687 APP-BP1, a novel protein that binds to the carboxyl-terminal... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:8626687 APP-BP1, a novel protein that binds to the carboxyl-terminal region of the amyloid precursor protein. |
| GO:0004867 serine-type endopeptidase inhibitor activity | IDA PMID:10652580 Production of amyloid beta protein precursor as a proteinase... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:10652580 Production of amyloid beta protein precursor as a proteinase inhibitor by human astrocytic tumors. |
| GO:0009986 cell surface | IDA PMID:7593229 Serine proteinase inhibitors in human skeletal muscle: expre... | ACCEPT | Summary: IDA annotation based on direct experimental assay. Reason: IDA annotation supported by direct experimental evidence. Supporting Evidence: PMID:7593229 Serine proteinase inhibitors in human skeletal muscle: expression of beta-amyloid protein precursor and alpha 1-antichymotrypsin in vivo and during myogenesis in vitro. |
| GO:0005886 plasma membrane | TAS PMID:10806211 Phosphorylation of the beta-amyloid precursor protein at the... | ACCEPT | Summary: TAS annotation based on author statement in referenced publication. Reason: TAS annotation supported by literature. Supporting Evidence: PMID:10806211 Phosphorylation of the beta-amyloid precursor protein at the cell surface by ectocasein kinases 1 and 2. |
| GO:0005515 protein binding | IPI PMID:10081969 Molecular cloning of human Fe65L2 and its interaction with t... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:10081969 Molecular cloning of human Fe65L2 and its interaction with the Alzheimer's beta-amyloid precursor protein. |
| GO:0005515 protein binding | IPI PMID:10049767 X11L2, a new member of the X11 protein family, interacts wit... | MARK AS OVER ANNOTATED | Summary: IPI protein binding annotation. Generic protein binding does not provide specific functional information. Reason: Generic protein binding uninformative - should use more specific MF terms. Supporting Evidence: PMID:10049767 X11L2, a new member of the X11 protein family, interacts with Alzheimer's beta-amyloid precursor protein. |
| GO:0098631 cell adhesion mediator activity | TAS file:human/APP/APP-uniprot.txt | NEW | Summary: NEW annotation proposed in this second-pass review. Full-length APP functions at the neuronal cell surface as an adhesion/receptor-like molecule that promotes cell-cell contact and synaptogenesis. Reason: This molecular function is already used in the APP core-function synthesis but was missing from the existing annotation block. It captures full-length APP biology more directly than generic cell adhesion process terms. Supporting Evidence: file:human/APP/APP-uniprot.txt Functions as a cell surface receptor file:human/APP/APP-uniprot.txt neuronal adhesion and axonogenesis |
| GO:0050839 cell adhesion molecule binding | TAS file:human/APP/APP-uniprot.txt | NEW | Summary: NEW annotation proposed in this second-pass review. APP molecules and APP-family ectodomains participate in adhesion-associated interactions at the cell surface and synapse. Reason: This term is present in the APP core-function synthesis but absent from GOA-derived annotations. It represents APP adhesion-associated binding better than generic protein-binding annotations. Supporting Evidence: file:human/APP/APP-deep-research-falcon.md cell adhesion file:human/APP/APP-uniprot.txt promotes synaptogenesis |
| GO:0005507 copper ion binding | TAS file:human/APP/APP-uniprot.txt | NEW | Summary: NEW annotation proposed in this second-pass review. APP and amyloid-beta fragments bind copper through extracellular metal-binding regions and are linked to copper reduction/homeostasis. Reason: Existing annotations include broad metal and transition-metal binding, but the APP core-function synthesis uses the more specific copper ion binding term. UniProt supports copper binding/reduction directly, so the specific MF term should be represented. Supporting Evidence: file:human/APP/APP-uniprot.txt Extracellular binding and reduction of copper file:human/APP/APP-uniprot.txt Amyloid-beta peptides are lipophilic metal chelators |
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Download this section (compressed HTML)Q: Which APP isoforms and proteolytic fragments mediate normal in-vivo synaptic adhesion, neurite outgrowth, and axon guidance in adult neurons versus development?
Suggested experts: APP neurobiology expert, synapse development expert, neuronal cell-adhesion expert
Q: What endogenous receptor or partner mechanisms mediate sAPPalpha trophic signaling in vivo, and which functions are separable from full-length APP cell-adhesion activity?
Suggested experts: APP processing expert, neurotrophic signaling expert
Q: How do APP copper and zinc binding or redox activities operate under physiological neuronal and endosomal conditions, and which functions belong to full-length APP versus amyloid-beta fragments?
Suggested experts: neuronal metal homeostasis expert, APP biochemist
Q: Which APP intracellular-domain transcriptional or signaling effects are direct evolved signaling functions rather than secondary consequences of altered trafficking or proteolysis?
Suggested experts: APP intracellular signaling expert, neuronal trafficking expert
Experiment: Compare endogenous APP isoform and fragment rescue in APP-deficient neurons or knock-in mice, separating APP695 from KPI-containing APP751/770 and measuring synapse formation, neurite outgrowth, axon guidance, and plasticity.
Hypothesis: Distinct APP isoforms and cleavage products make separable physiological contributions to adhesion, trophic signaling, and axon/synapse development.
Type: endogenous rescue and isoform-specific knock-in genetics
Experiment: Generate cleavage-resistant and fragment-selective APP alleles at the endogenous locus to separate full-length adhesion, sAPPalpha trophic signaling, amyloid-beta production, and APP intracellular-domain functions in vivo.
Hypothesis: Full-length APP, soluble ectodomain, amyloid-beta, and intracellular fragments each account for different subsets of the observed neuronal phenotypes.
Type: knock-in allele series with in-vivo phenotyping
Experiment: Test APP copper/zinc-binding-site mutants at endogenous expression levels while measuring neuronal metal homeostasis, redox state, endosomal physiology, synaptic function, and APP trafficking.
Hypothesis: APP metal-binding motifs contribute to physiological neuronal metal/redox homeostasis independently of overexpression or aggregate toxicity.
Type: endogenous mutagenesis with biochemical and physiological assays
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